| 00:00 | very good. So this is neuroscience six. It's Monday September 12 and |
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| 00:11 | gonna start talking about the action And you have two more lectures after |
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| 00:18 | that will cover new material. You have midterm one review and then you |
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| 00:22 | have your midterm on 26 September which Monday. So all of the information |
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| 00:30 | on the exams and everything can be on on your syllabus which is on |
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| 00:35 | blackboard. So you can always check there. Uh you can always review |
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| 00:41 | videos on video points dot org. . And that should help you catch |
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| 00:50 | with any material you may have And what we discussed last time was |
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| 00:59 | membrane potential or neuronal membrane potential And as we talked about it, |
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| 01:08 | also talked about several important aspects. in particular, we actually introduced this |
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| 01:16 | which is your patella tendon, knee reflex circuit. And we pointed out |
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| 01:22 | three subtypes of cells involved in there how the circuit works. So you |
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| 01:27 | be responsible for knowing the three cell their morphology, their neurotransmitters within the |
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| 01:34 | inhibitory and what their functions are in circuit. And then we moved on |
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| 01:41 | talk about how you have a separation charge across plasma membrane and that means |
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| 01:48 | there is uneven distribution of different So we talked about how these ions |
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| 01:56 | cross through plasma membrane and for them cross through plasma membrane you need |
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| 02:02 | And those channels, protein channels in case and the protein channels that we're |
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| 02:08 | about when we're talking about resting membrane and today about the action potential. |
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| 02:14 | voltage independent of voltage gated channels. Liggins do not bind to these channels |
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| 02:20 | regulate the flocks of sodium potassium and . But these channels are built out |
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| 02:25 | the politics chains that turn themselves into co ordinary structures of sub units coming |
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| 02:34 | , forming a channel poor and these are selective for a specific ion. |
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| 02:41 | sodium channel is controlling and regulating the of sodium coming from outside to |
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| 02:49 | potassium channel is regulating the amount of going from inside to outside. We've |
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| 02:56 | that these are selected filters and the properties are based partly on size on |
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| 03:03 | size of the waters of hydration which uh inverse to the size of an |
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| 03:10 | and also the interactions with amino acid . So when these polyps peptide chains |
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| 03:17 | formed, some of these amino acids the polarity, negative positive polarity. |
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| 03:23 | these negatively charged polar groups mean assets interact in this case with sodium ion |
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| 03:31 | the positively charged amino acid group would with an an eye on such as |
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| 03:37 | for example. And so these channels be selective and the pumps will utilize |
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| 03:46 | A. T. P. And pumps will always pump potassium and sodium |
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| 03:52 | concentration gradient, which imply that a of what passes through the channel does |
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| 03:59 | on concentration gradient but the concentration of gradient alone cannot account for the floor |
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| 04:07 | the ions that actually carry a So this is we talked about how |
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| 04:15 | attract. So sodium Cantons will be to the negative cathode and chloride and |
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| 04:23 | will be attracted to an O. equally so positive sodium charge of positive |
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| 04:30 | charge will be repelled by the life . And in order for this uh |
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| 04:41 | of charge to happen, you need , you need channels to be |
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| 04:47 | And there is a certain rules by I also go to cross through these |
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| 04:53 | , not just based on selectivity but based on the voltage in the |
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| 04:58 | In this case the system is the recall that the membrane is charged but |
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| 05:05 | inside of the cell or the cytoplasmic core of the cell or the extra |
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| 05:12 | fluids are charge neutral. So this of charge and this activity and all |
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| 05:19 | the action and action potential will discuss happening at the level of the |
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| 05:26 | And what we discussed is that concentration not enough. And so we have |
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| 05:34 | equilibrium potential and equilibrium potential is if have a sodium channel and you have |
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| 05:39 | lot of sodium on one side and sodium on the other side. The |
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| 05:44 | will start flexing but it will never out in its concentration because this positively |
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| 05:52 | build up of sodium ions will start its own for the influx of that |
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| 05:58 | sodium ion. So we talked about this is not just for sodium or |
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| 06:04 | . These rules apply to all of ions and the point at which the |
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| 06:11 | force the concentration gradient is driving ion one direction and that force is equal |
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| 06:19 | the charge, the electrical force driving or repelling in this case into the |
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| 06:25 | direction to the concentration gradient force, forces are equal and you have what |
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| 06:30 | called the equilibrium potential, we know known concentrations of the major ions. |
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| 06:36 | have a lot of sodium chloride on outside of the south. You also |
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| 06:41 | a lot of calcium on the outside the cell compared to the inside of |
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| 06:45 | cell. And potassium is dominating on inside of the cell. So we |
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| 06:51 | that you can remember these actual Malamala if you want to but you should |
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| 06:57 | them for the exam with these four or you can actually remember the approximate |
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| 07:05 | on the outside versus inside. But you remember the sodium chloride is abundant |
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| 07:10 | on the outside of the south and lot of calcium and on the inside |
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| 07:15 | potassium and you can memorize and learn things easier. And as we discuss |
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| 07:21 | knowing the concentrations of ions and some variables involved, we can actually |
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| 07:28 | We can actually calculate the reversal potential equilibrium potential for each one of the |
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| 07:38 | . And so we went on to about nine ERnst equation and ERnst equation |
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| 07:43 | particular focuses on a single ionic And when you calculate equilibrium potential or |
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| 07:49 | potential for sodium, it's for sodium potassium is for potassium. So we |
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| 07:56 | how you have these variables are how you have the gas and electrical |
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| 08:04 | , that disease of aliens. So dive alien cat ions, calcium two |
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| 08:09 | it will be divided by two and log base 10 of ion outside versus |
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| 08:16 | . So it's for sodium. You in the sodium values of these concentrations |
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| 08:22 | the outside versus inside. If it's you put the concentrations on the outside |
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| 08:29 | inside for potassium and so on. as you do this calculation, you |
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| 08:35 | these are T C F 2.3 into million balls. You take a log |
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| 08:41 | the concentrations depending on the valance, number may become minus 61 for |
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| 08:48 | which is minus one. That number diving is half 30.77 because you're dividing |
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| 08:55 | by two here and these concentrations will you to calculate individual equilibrium potentials. |
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| 09:03 | so I also said that there is little bit of disparity and difference. |
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| 09:08 | what is the equilibrium potential value for versus sodium versus calcium versus chloride as |
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| 09:16 | differs in different textbooks. And we back to the same concept that I |
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| 09:22 | that even resting membrane potential amongst the of the south will have slightly different |
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| 09:28 | of what the resting membrane potential value . That is partly dependent on |
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| 09:36 | The openings of the channels. Talk thermodynamics. The heat makes molecules move |
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| 09:41 | in and out. Okay. And course the concentration, the electrical charge |
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| 09:47 | arts potential, all of these things will will contribute to the potential. |
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| 09:53 | it's for single ion. And when talking about the membrane potential, the |
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| 09:58 | potential is now calculated by taking into not just one ion but potassium or |
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| 10:06 | . You actually have to take into several ions. So to calculate numbers |
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| 10:11 | town shaw, we also need to into account the permeability of that given |
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| 10:16 | . So PK value here is a for potassium channel. P. |
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| 10:21 | A stands for premium ability for sodium . How permeable are these channels And |
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| 10:27 | and resting membrane potential. This is the faith of neurons. They have |
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| 10:31 | lot of potassium channels and those potassium are leaky. That means that they're |
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| 10:36 | and a lot of potassium is slowly from inside of the cell into the |
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| 10:41 | of the cell. And so the number and potential is dominated with potassium |
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| 10:48 | potassium this is permeability for potassium is times greater than it is for |
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| 10:55 | This is addressed when the cell is being activated by too much inputs coming |
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| 11:00 | , not much activity. And so have a number of potential. A |
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| 11:04 | membrane potential value of minus 65 million . But I mentioned to you that |
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| 11:10 | you look here, it says minus to minus 75. So you have |
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| 11:15 | some maybe local changes and fluctuations and species the way their distributed outside the |
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| 11:22 | , there are certain circuits, there's organs sensory organ, for example, |
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| 11:27 | the organ of corti in the When we study the auditory system, |
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| 11:31 | realize that it's surrounded by endo extra cellular fluid that's very high in |
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| 11:38 | and these extra cellular fluids are very in sodium and intracellular fluids are higher |
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| 11:44 | . So therefore you will see slight in the potentials. But I'll explain |
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| 11:49 | you how to prepare yourself with exam . And it is not to trick |
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| 11:53 | by asking you is the number of between minus 60 to minus 73 or |
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| 11:58 | minus 60 minus 75. I'll give a clear descriptions of those that I |
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| 12:04 | stick to buy for the test. , on top you have nurse |
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| 12:11 | on the bottom you have Goldman So on top of your calculating e |
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| 12:18 | , which is the equilibrium potentials for ions or reversal potentials. And I'll |
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| 12:23 | you what I call the reversal potentials and then the bottom you're calculating the |
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| 12:28 | number of potential. So what happens permeability for sodium goes up? The |
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| 12:41 | for sodium goes up and for potassium down who is going to influence the |
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| 12:46 | potential? More potassium or sodium mm , whoever the membrane is more permeable |
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| 12:52 | that ion permeability ratio, of you have to still take into consideration |
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| 12:56 | concentrations. But permeability could be one the main driving force is shifting permeability |
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| 13:03 | potassium, shifting the membrane potential toward equilibrium potential for potassium During the rising |
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| 13:12 | of the action potential, the cell 20 times more permeable to sodium. |
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| 13:18 | what is sodium going to drive? is trying to do and drive the |
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| 13:23 | of potential to its own equilibrium potential . So you will see that the |
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| 13:29 | potential for sodium is positive 62. so the resting membrane or the overall |
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| 13:36 | potential is gonna shift from negative 65 negative 45 to positive 20. And |
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| 13:42 | because sodium becomes the most dominant and most permeable membrane ion, local concentrations |
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| 13:51 | these islands can change temporarily, but pretty well controlled spatially and temporally. |
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| 13:59 | don't want too much calcium to go locally. Too much sodium analysis. |
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| 14:04 | much potassium on the outside. So a balance and glee ourselves such as |
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| 14:12 | control and regulate the overall concentrations of and even neurotransmitters that we'll talk later |
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| 14:21 | this course, this diagram on the actually illustrates that this is extra cellular |
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| 14:30 | on the outside and we know that don't have much potassium on the outside |
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| 14:33 | the cell, most of the potassium on the inside of the south And |
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| 14:38 | shows that from the resting membrane potential regular level of potassium on the outside |
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| 14:44 | about 3.5 to 5 million moller So this is your X axis and |
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| 14:51 | Y axis is the number of And what it illustrates is that if |
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| 14:58 | change the concentration of potassium on the from 5 10 15 20 what happens |
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| 15:11 | you de polarize the member your d the membrane. So local changes in |
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| 15:21 | concentrations in this case is with It's a very classical case of how |
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| 15:26 | can make cell membranes more excitable by potassium on the outside of the |
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| 15:31 | It's used in many departments. It's in electrophysiology studies. It's called you |
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| 15:37 | applying high potassium and biochemistry studies protein stimulating cells with potassium chloride high concentrations |
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| 15:46 | activate themselves. What it does, what it does for neurons is outside |
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| 15:52 | and outside potassium concentrations will drive this in potential and if it drives the |
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| 15:58 | of potential passed this -45 million volts . It will make cells fire action |
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| 16:05 | . So this graph illustrates how extra potassium increases from normal regular extra cellular |
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| 16:13 | 3.55 million million moller to 10 15 moller you're causing a significant 10 to |
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| 16:21 | million dol de polarization shift in the . So this cannot just happen that |
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| 16:29 | potassium concentrations go up let's say you a leaky blood brain barrier and you |
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| 16:35 | consume very high potassium drinks a lot potassium got into your bloodstream and it |
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| 16:41 | control. But now a lot of leaked in locally someplace into the |
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| 16:45 | Or potassium also spills when there is lot of activity in the cells. |
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| 16:50 | potassium that goes up and then other get excited by that potassium going |
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| 16:55 | Not even synaptic communication by by chemical in potassium levels. Astrocytes their function |
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| 17:04 | their morphology allows for buffering spatially circulating or redistributing these abnormal local potassium |
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| 17:18 | slurping it up. They have the network of processes astrocytes astrocytes are also |
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| 17:26 | to other astrocytes. And you learn the second half of this course that |
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| 17:31 | are electrical junctions and gap junctions through these astrocytes can pass ions to other |
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| 17:38 | number into membranes. So they're perfect taking out these locally increases concentrations of |
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| 17:48 | temporary hopefully. And to prevent any to prevent sustained the polarization of the |
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| 17:55 | where the cells become more and more , where they can become hyper |
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| 18:01 | What you do is you slurp up potassium, you redistribute it spatially through |
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| 18:06 | own processes with them astra site and pass it on to the interconnected |
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| 18:12 | Great again positioning because the ostracized if recall the position around the synopsis and |
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| 18:20 | around the blood brain barrier, the positioning, great morphology, extensive morphology |
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| 18:28 | buffering spatially buffering and equalizing of these local rises and for example, potassium |
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| 18:37 | in this case in your book, is a really uh great story and |
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| 18:46 | is a section of that discovery that about different scientists and how they got |
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| 18:52 | be where they are and what two discovery or pathway of discovery they |
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| 19:02 | or how they contributed to things. so What what what was interesting in |
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| 19:08 | 80s and 90s was to understand the structured re dimensional structure of these |
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| 19:16 | So there are very complex these polyp , tertiary conflicts is forming into corporate |
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| 19:23 | interacting with each other. And roderick is one of the scientists and medical |
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| 19:30 | that is described in this pattern of . So he's an MD and he |
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| 19:35 | that he's going to seek an answer what exactly does potassium channel structure look |
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| 19:43 | . So, in any scientific quest if you are passionate about any science |
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| 19:50 | any disease or any solution or you have to have a problem that |
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| 19:58 | want to solve. And so here's indeed decides that he's gonna, instead |
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| 20:04 | treating patients actually gonna solve the structure the potassium channels, how would you |
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| 20:12 | that? Somebody told you sell the , what do you do remember in |
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| 20:19 | 80s there was Internet but the first kind of didn't find their way into |
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| 20:26 | until Mid 90s on, you a pretty regular basis. So you're |
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| 20:34 | talking pre kind of a digitization age you may if you may, it's |
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| 20:39 | there but not exactly we use but he decides that he's gonna uh study |
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| 20:48 | and he picks fruit flies as a . So the next thing is what |
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| 20:53 | the system? What is your His objective, I want to know |
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| 20:58 | structure with capacity channel. So why he just go into human brain and |
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| 21:02 | a piece and look at why is using flies? Because fruit flies will |
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| 21:08 | fast and you can do genetic mutations fruit flies and you can target certain |
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| 21:21 | assets sequences in this polyp peptide through mutations. That's not all um why |
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| 21:30 | you take a model of like a fly? And think that this |
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| 21:37 | this model is going to mean something humans because we have conserved sequences of |
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| 21:46 | assets. Alright, we have hm to warms like 70% Hamal Aji proteins |
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| 21:56 | so there's a certain sequence and we that the genes express the sequence code |
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| 22:06 | this sequence proteins from messenger RNA, you get the production translation to |
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| 22:15 | So um okay, is all of important if if all of these subunits |
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| 22:27 | here are all of the parts of structure is important Or is there one |
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| 22:37 | corner stone, is there key parts this channel that you want to know |
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| 22:45 | . If you want to solve the of the channel, you also have |
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| 22:48 | think about why you're solving the structure the channel because I want to know |
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| 22:53 | it opens and closes. I want know what opens it and what closes |
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| 23:01 | . And I also have a hypothesis certain parts of this channel are more |
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| 23:06 | than other parts, therefore mutating the lumen of the channel targeting this, |
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| 23:14 | the cytoplasmic or the extra cellular size the channel, which ones are |
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| 23:21 | So he goes on this hunt and this hump. He uses shaker |
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| 23:25 | genetic mutations and toxins and he uses particular spider toxins. Because toxins in |
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| 23:34 | , small molecules by small animals, spiders that have very potent binding properties |
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| 23:42 | these channels. And yes, they kill little flies and they can kill |
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| 23:47 | humans too. Again, there's similarity . And so the sequences that you're |
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| 23:54 | find destruction, you're gonna find the important sequences to keep this channel closed |
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| 23:59 | open. You're gonna now understand what this channel, what causes the channel |
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| 24:05 | ? What causes the closure? How toxins in nature or chemical toxins can |
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| 24:12 | these channels. So he uses toxins side directed me to genesis, |
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| 24:21 | is directing it to specific sites the to genesis the mutations, the specific |
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| 24:28 | of this. And he actually starts by targeting certain sequences. He starts |
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| 24:38 | the three dimensional structure of the structure this of this channel but that's not |
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| 24:45 | for him and he actually now has quest to visualize this channel. So |
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| 24:53 | says I've done enough work with shaker . They're called shaker flies because if |
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| 24:59 | mutate potassium channel in those flies they start shaking and guess what humans that |
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| 25:04 | mutations or potassium channels. Some of same mutations will exhibit seizures or epileptic |
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| 25:12 | behavior. So he's used, Shake gene mutations, targeted different sequences with |
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| 25:20 | mutations targeted different parts of the different toxins to see which ones bind |
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| 25:25 | the potassium channels, which ones may interacting with specific sequences in the potassium |
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| 25:30 | . And so he now exits out that lab and goes to different university |
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| 25:35 | opens a new lab for X ray . Mhm. His quest is not |
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| 25:44 | learn how to be an electric His quest is to see the structure |
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| 25:50 | the potassium channel. So if you the shaker flies and use the |
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| 25:57 | you'll use toxins, will use the and you still can't get a full |
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| 26:02 | . And so at that on the ray crystallography becomes something that is becoming |
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| 26:09 | . The biochemistry departments where you actually a single curtain inside the crystal, |
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| 26:16 | trap a single protein inside the crystal you have X rays exposing right crystallography |
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| 26:28 | trap pro dam and you can actually the three dimensional structure using the X |
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| 26:34 | crystallography but to go from being an physiologist. And nd who now is |
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| 26:43 | electro physiologist and geneticist and behaviorist because has to observe the fly behavior and |
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| 26:51 | up flies electro physiologist. He adds thing onto his roller dex is that |
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| 26:59 | is an X ray crystallography. And he told his colleagues that I'm gonna |
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| 27:04 | start doing actually crystallography, they looked him like you know you're not, |
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| 27:10 | know why your dentist, why do wanna be a nose throat doctor on |
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| 27:15 | of that? You know being dentist nothing for him. It's not for |
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| 27:21 | , it's solving the problem. And this case the problem is I want |
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| 27:25 | know what potassium channel looks like and it is regulated and what are the |
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| 27:29 | pieces or segments of this channel. I said that before you guys are |
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| 27:37 | a quest, you're very much thinking you're an undergraduate is that your quest |
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| 27:42 | for degrees and that is true in in many instances where you have to |
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| 27:49 | basic training, you have to get degrees in order to get better at |
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| 27:53 | quest. But the ultimate quest is passion to solve the problem, how |
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| 28:02 | gonna get there. If it's going take you six years of bachelors, |
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| 28:06 | years of Bachelors, five years of , seven years of post off, |
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| 28:12 | years of masters, it is completely to you how you gonna get to |
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| 28:19 | desired solution for a problem. And you have that in front of |
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| 28:24 | I think it is going to make journey more interesting because it is about |
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| 28:28 | journey, remember that it's forward. straight. And there's also backwards. |
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| 28:35 | , you know, you fall we have to get up but it's |
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| 28:38 | . And then when you go what happens, you always come from |
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| 28:44 | and it doesn't mean that if you left, you cannot come back with |
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| 28:47 | same cross where you actually can and you can go forward or in that |
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| 28:52 | to the other direction. Okay, this is a great story for me |
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| 28:57 | I think it should be a great for you. And that's something you |
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| 29:00 | keep in mind too. There's a uncertain times With with degrees with bachelors |
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| 29:08 | , with the viruses, with all these things. But I encourage you |
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| 29:11 | think about something that you feel passionate and this is your really end goal |
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| 29:19 | how you get there and forget it's take you 12 years. So what |
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| 29:23 | is, don't lose that the side that, you know, of that |
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| 29:28 | . And sometimes it changes too. it changes great story nonetheless. And |
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| 29:36 | we're going to start talking about the potential and you're gonna learn everything. |
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| 29:40 | spend most of the time on this membrane potential value, which is the |
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| 29:45 | is fluctuating very slowly from a little deep polarized, a little bit hyper |
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| 29:51 | , but it's staying around the resting potential. If the cell d polarizes |
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| 29:56 | and produces the action potential, you're have the rising phase of the action |
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| 30:02 | to overshoot the following phase of the potential. The undershoot and then re |
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| 30:07 | back to the resting membrane potential. gonna know more than you wanted to |
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| 30:12 | about the action potential when we're through this And next week. So as |
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| 30:18 | as I said, the first thing you will see if you plug an |
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| 30:23 | inside the cell addressing membrane potential, will see a change of minus 65 |
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| 30:28 | volts. But if you're recording an potential, you will see a very |
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| 30:32 | change from about minus 65 million 70 to 100 mil of all changed |
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| 30:38 | plus 40 plus 20 and then re . You can record action potentials intracellular |
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| 30:44 | as is shown here. Or you also pick up action potentials extra cellular |
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| 30:49 | . So some electorates will pick up action potential from outside the south, |
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| 30:53 | if the position close to the excellent segment which will be producing the action |
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| 30:59 | . Okay, But the amplitude of extra cellular recorded action potential is going |
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| 31:04 | be much much smaller because it's really like a little antenna listening to what |
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| 31:10 | inside the cell if you're listening to outside the cell. So like something's |
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| 31:14 | on inside the room, two people and listening outside the room, you |
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| 31:18 | barely hear and decide the words. , uh in your lecture notes, |
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| 31:34 | have this really cool video that we're to watch the carefully pods. Body |
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| 31:54 | and habits are so very different from of humans that there might almost be |
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| 31:58 | from another world. So perhaps it's surprising that it took a long time |
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| 32:04 | scientists to discover that there are fundamental between the nervous systems of pods and |
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| 32:15 | . Yet it was the recognition of useful difference in their nervous system, |
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| 32:19 | enabled scientists to undertake research that has to a growing understanding of the mechanisms |
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| 32:25 | our own nervous system. The breakthrough the nerves that control the contraction of |
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| 32:31 | mental muscles used in jet propulsion. this archive film shows by simultaneously contracting |
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| 32:40 | mental muscles. Even a moderately sized can inject a huge amount of water |
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| 32:45 | great force. In the mid 19 , the british zoologist Professor James Young |
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| 32:55 | engaged in a study of the squid's . Young observed an array of large |
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| 33:02 | structures, each as much as a in diameter, in the squid's mantle |
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| 33:08 | these structures were never filled with They could not have been blood vessels |
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| 33:13 | their similarity to surrounding nerve fibers. thought they must be single neurons. |
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| 33:18 | axons, they're transmitted nerve impulses from concentration of nervous tissue called a ganglion |
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| 33:24 | the mantle muscles using electrodes, he the surrounding nerve fibers and found that |
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| 33:35 | could only produce large muscle contractions in metal when the large tubular structures remained |
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| 33:47 | . So these were indeed, giant . Scientists quickly appreciated the significance of |
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| 33:57 | finding for here at last was an , large and robust enough to investigate |
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| 34:02 | the techniques available at the time and that survived for several hours when isolated |
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| 34:07 | the nucleus, the intracellular contents of giant axon could be removed and |
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| 34:17 | leading to the discovery that sodium ions more concentrated outside the nerve cell and |
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| 34:23 | ions more concentrated inside by refilling the axons with solutions of precisely known chemical |
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| 34:33 | . Experimenters were able to unravel the of, do you remember when we |
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| 34:37 | about ectoplasmic transport, and I mentioned it was first to study the slow |
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| 34:44 | ectoplasmic transport. They used the guys inject and see how fast they |
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| 34:50 | So these were some of these initial , experimenters were able to unravel the |
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| 34:55 | of iron transport across the membrane. giant axons are large enough and robust |
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| 35:06 | for fine electrodes to be inserted through cell membrane and into the axa |
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| 35:18 | In these early techniques, a fine tube was first inserted into the axon |
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| 35:23 | secured with thread. Then the tube used to introduce a fine wire electrode |
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| 35:49 | which the voltage between the inside and outside could be measured, But the |
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| 35:55 | of the Nerve Impulse was far too for detailed study with any of the |
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| 36:00 | measuring devices of the late 1930s. wasn't until the 1950s following the wartime |
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| 36:08 | of electronic equipment such as the cathode Oscilloscope. That major progress was |
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| 36:16 | Scientists found that the nerve impulse was as a characteristic wave of electrical potential |
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| 36:23 | that this all or nothing action potential generated mainly by transient movements of sodium |
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| 36:28 | potassium ions across the nerve membrane. on the squid giant axon unravel the |
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| 36:38 | of the formation and propagation of the action potential. This understanding led directly |
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| 36:44 | the development of drugs that block action formation And so act as local anesthetics |
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| 36:50 | used routinely as painkillers in dentistry and surgery. Anybody cares to guess what's |
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| 36:57 | local anesthetic used in dentistry? Minor . Nobody had a drill their tooth |
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| 37:06 | had a crown lidocaine, no Everybody has really good teeth, |
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| 37:18 | Alright so this was the early days discovery of the action potentials and recording |
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| 37:26 | these action potentials. And so when think about the squid, giant axon |
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| 37:34 | , the squid is not that It's not like a squid coming out |
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| 37:37 | the scene swallowing the ship but it's the axon is giant because it's one |
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| 37:44 | in diameter, One millimeter is 1000 meters and a C. M. |
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| 37:55 | . Act song neuronal axon is approximately micro meter In diameter. So 1000 |
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| 38:05 | smaller. Basic one 1000 times Um So only um I would say |
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| 38:19 | in the Late 70s and 80s is people were able to record from single |
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| 38:28 | and c. n. s. animals like Rats and Mice. And |
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| 38:36 | yeah So this is all pretty new . If you remember if you stimulate |
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| 38:43 | neuron, if you inject positive charge gonna de polarize this neuron and you're |
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| 38:48 | record a certain number of action If the cell doesn't de polarize to |
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| 38:56 | threshold for action potential which is the for action potential values about 45 million |
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| 39:04 | , the cell will not respond with potentials. So with this shows on |
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| 39:11 | top are the square wave stimulations that coming from the electrodes. So this |
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| 39:17 | on positive charge coming in off positive stops as you can see the cell |
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| 39:24 | with the surrounded rounded responses. So takes a minute it doesn't reach a |
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| 39:31 | charge right away. It takes a for this charge to build up around |
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| 39:35 | membrane. And that's because the plasma has resistance and it also has capacitance |
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| 39:41 | that will discuss. Also we won't those. Um Now the important part |
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| 39:48 | that if you inject more current and reaches the threshold for action potential generation |
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| 39:54 | will generate a certain number of action . And if you give it even |
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| 39:59 | stimulus that number of action potentials is be even greater. So in the |
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| 40:07 | as I mentioned to you already, strength of the stimulus is reflected by |
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| 40:14 | number or the frequency of the action . And sometimes the patterns of these |
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| 40:18 | potentials. That's so what are some the things that we are going to |
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| 40:29 | and that you should know? This one of the concept that is called |
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| 40:33 | driving force already mentioned it in previous . But ionic driving force, if |
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| 40:40 | remember the equals Ir I is equal over hard, But G is equal |
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| 40:53 | over R. So I is equal times V. Everybody sees that V |
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| 41:02 | Ir y equals B over R. conductance is inverse of the resistance to |
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| 41:11 | . This is the current for potassium equal to the conductance for potassium times |
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| 41:19 | driving forms. And the driving Fords the difference between member and potential which |
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| 41:27 | calculated using Goldman equation and the equilibrium for potassium, which is calculated is |
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| 41:37 | the greater the difference between the membrane overall number and potential and the equilibrium |
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| 41:45 | for that ion the greater is the force. The greater is the current |
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| 41:54 | it depends on the conducts again. this is not just for compassion for |
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| 41:59 | ion current. I is equal finds the driving force for that |
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| 42:06 | So here, for example, we a number in potential that is at |
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| 42:12 | mila bolts. This is uh an , it's zero mila bolts. All |
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| 42:18 | channels are closed and you have sodium in blue and potassium channels in in |
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| 42:26 | pink. Mhm. Now potassium starts from the south in a positive |
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| 42:35 | Leaving makes the inside or the membrane more negative. So now at this |
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| 42:46 | here when all the channels are the conductance for potassium are in fact |
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| 42:53 | for any ion is zero. And are the equilibrium potential values of potassium |
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| 42:59 | equilibrium potential values for sodium. So current for potassium which is G. |
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| 43:08 | . Which is zero times the driving is equal zero. There's no current |
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| 43:13 | for potassium, there's no current here civil the channels of clothes. What |
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| 43:19 | if you open potassium channels, potassium going to go from inside of the |
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| 43:23 | to outside of the cell. Leaving sell more negative As it leaves the |
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| 43:31 | more negative. The driving force for is greater than zero And the conductance |
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| 43:39 | greater than zero. Therefore you have current that is greater than zero. |
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| 43:45 | you go to -80 the potassium is leaving, leaving what what is the |
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| 43:53 | 80 value here on the volt meters 80 and the eks minus 80. |
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| 44:02 | what do you have here? What the difference between the member and potential |
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| 44:07 | the delivery and potential for potassium -80 ? What's The Difference Here? |
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| 44:16 | So at this point G K. greater than zero. That means there's |
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| 44:22 | flux of potassium conductance is happening. driving force Vienna minus C. |
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| 44:30 | Zero. Therefore the net current or current for potassium is also zero. |
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| 44:38 | this illustrates to you how the current on the conductance. You have conductance |
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| 44:46 | the channel and the difference between member potential equilibrium potential driving force for that |
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| 44:54 | . So here you have a great between let's say minus 20 to minus |
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| 44:59 | . You have a great driving force and you have the channels open. |
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| 45:04 | there's gonna be a lot of current through. But even if the channels |
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| 45:08 | open and you have conductance but the potential G. M. Is the |
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| 45:16 | as the equilibrium potential. This value zero and the current overall current for |
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| 45:23 | is also zero. So what does tell you? That tells you that |
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| 45:29 | single ion that has its own nurse equilibrium potential that drive for that ion |
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| 45:39 | depend how close or how far away overall number of potential which is other |
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| 45:46 | species flexing sodium potash in florida. the some of these. How where |
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| 45:51 | the value of this equilibrium potential? is the value of the membrane |
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| 45:57 | The greater the separation between VM and liberal potential. The greater is the |
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| 46:03 | force the to come the same There's no driving force and there's no |
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| 46:10 | con flux for that island. And I mentioned the ions that are |
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| 46:18 | addressed our potassium ions that we talked because we have leaky potassium channels and |
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| 46:24 | conductance is away way greater than sodium is. But as you open up |
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| 46:30 | little bit of the sodium channels, plasma membrane de polarizes. And as |
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| 46:37 | d polarizes that this rising phase of action potential, the membrane conductance is |
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| 46:44 | dominated by sodium. So the sodium is much greater than potassium conductors that |
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| 46:53 | again during the falling phase of the potential. What what is happening is |
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| 47:03 | the cell is leaking to potassium, trying to keep the overall and dominate |
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| 47:09 | overall number of potential close to its equilibrium potential value which is negative |
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| 47:15 | So keep it hyper polarized and sodium the sodium channels open is trying to |
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| 47:22 | the overall membrane potential. So this all B. M. This is |
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| 47:27 | one I oh this is all M. Tries to drive the overall |
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| 47:30 | potential to its own equilibrium potential which way positive positive 62. So it's |
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| 47:38 | . And then that domination switches sodium channels close and potassium channels now |
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| 47:44 | a huge driving force because the member potential here at the peak of the |
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| 47:50 | potential is far away from the equilibrium for potassium which is minus 80. |
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| 47:56 | it's dominated again by conductance is with until it gets re polarized with |
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| 48:02 | A. K. A. P. A. S. The |
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| 48:05 | re polarize the member and potential to resting membrane potential value. And so |
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| 48:12 | also goes back to the goldman I said that wrestling number and potentially |
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| 48:17 | 40 times more from the ability to versus sodium. Now you can clearly |
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| 48:23 | that the permeability during the rising phase action potential is dominated. The membrane |
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| 48:29 | that are open are sodium channels and by sodium flux and then re polarization |
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| 48:35 | the following phase of action potential is with the potassium flux again, so |
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| 48:42 | permeability, what is member and most to depends on voltage, the fluxus |
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| 48:48 | voltage and the voltage depends on the permeability of these different channels. And |
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| 48:56 | the relationship between equilibrium potential and the membrane potential is what determines the driving |
|
| 49:04 | for that. I'll so we're not go here yet but I'm gonna look |
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| 49:12 | something here. I think maybe it's your lecture notes. Yes. |
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| 49:27 | So we'll talk about this diagram and will be several questions in this diagram |
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| 49:33 | the concepts that we're discussing. Not this particular diagram, but the concept |
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| 49:39 | the action potential. But here I out the values for you and I'm |
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| 49:48 | ask you to know for the So I don't want you to know |
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| 49:52 | other textbook, some other exam question the textbook and resting number of |
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| 49:58 | We're gonna stick to these because if asked you what it is and you |
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| 50:01 | up in the book minus 70 to 75 I said this is minus 65 |
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| 50:05 | say no it's between minus 60 to 75. So let's do this. |
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| 50:11 | first of all we put this here is the number of potential, overall |
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| 50:15 | of potential and also the equilibrium potential . So liberal potential D. |
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| 50:20 | For potassium minus 90. And I recommend you either draw this or take |
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| 50:27 | good notes on it because as in example you recall the glial slide there's |
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| 50:34 | subtypes of glia can use that as great study tool right out all their |
|
| 50:39 | and potential dysfunctions or diseases they may involved in that. We've looked at |
|
| 50:44 | same here, you can take great on this and everything is already on |
|
| 50:49 | . So you can add onto it own explanations. A great study tool |
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| 50:54 | I would say probably the main one understanding the action potential. What is |
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| 51:00 | , what is coming in when it's out in the actual potentials potentials minus |
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| 51:06 | , liberal potential for potassium minus seventies chloride, resting membrane potential R. |
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| 51:13 | D. So you can decipher this 65 million bowls. So does that |
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| 51:18 | this membrane is gonna fluctuate around minus If it gets negative inputs is gonna |
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| 51:24 | hyper polarized. If it gets positive it's gonna get deep polarized. If |
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| 51:29 | gets negative inputs is gonna get hyper it gets positive inputs is gonna get |
|
| 51:35 | polarized if it gets a lot of inputs and that means a lot of |
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| 51:40 | synapses get activated onto a single dendritic spines and the soma as a |
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| 51:46 | lot of excited very input. Then membrane potential can reach the action potential |
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| 51:54 | value which is -45 million poles. at the point which the membrane potential |
|
| 52:01 | this action potential Value. Member and threshold value for action potential, it |
|
| 52:09 | produce an action potential. So it's all or none response. It's graded |
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| 52:15 | little bit of excitation, a bit in addition, a little bit more |
|
| 52:19 | . It's graded because these are post potential. So graded potentials. But |
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| 52:25 | the member in reaches -45, this all a non response. That means |
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| 52:30 | not great. That means that that will always produce a fluctuation from minus |
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| 52:35 | to plus 20 approximately sometimes minus 45 18, 45 minutes. Within the |
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| 52:42 | range, all or not, It's going to be small action potential. |
|
| 52:46 | size action potential, large size that always the same size all or |
|
| 52:52 | So what's happening here, we know the resting membrane potential, the potassium |
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| 52:57 | are open. They're leaking. So membrane is at minus 70 minus 75 |
|
| 53:02 | 65. It's really close to you'll say well it's also close to |
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| 53:07 | potential to floor ideas. Except that channels are closed. So, they're |
|
| 53:11 | very much relevant here. We're resting potential. Right? So now, |
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| 53:16 | we reach this value, this sodium channels open up in the cell |
|
| 53:23 | becomes mostly permeable to sodium. So massive influx of sodium sodium is coming |
|
| 53:31 | . What sodium is trying to sodium is trying to drive the overall |
|
| 53:37 | of potential VM to its own equilibrium value, it says to hell with |
|
| 53:46 | and membrane potential. All of my channels are open. I'm going to |
|
| 53:51 | equilibrium potential but it doesn't reach it the room potential for sodium because there |
|
| 53:58 | certain dynamics in the sodium channel that the channel close. And the other |
|
| 54:05 | , the other concept that we the closer the number of potential comes |
|
| 54:10 | the caribbean potential for sodium. This is the driving force. Remember, |
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| 54:18 | E K minus VM. For potassium N a minus V in sodium. |
|
| 54:26 | , address sodium has a great driving that the channels are not open. |
|
| 54:31 | are just the rules. But sodium actually has very small driving |
|
| 54:39 | Because in these positive potentials positive 20 thirties, just a little bit 20 |
|
| 54:46 | goal difference is the driving force becomes . So, because of these two |
|
| 54:51 | , the sodium channel kinetics about which will learn probably in the next |
|
| 54:57 | And because of the reduction of the force, the membrane dynamics switch again |
|
| 55:05 | the membrane becomes most permissible to potassium , the more deep polarization. More |
|
| 55:12 | channels open, more deep polarization. sodium channels open. So it's positive |
|
| 55:16 | move but it gets shut down by channel dynamics and the reduced driving force |
|
| 55:22 | potassium channels are really open and they're huge driving force. The difference here |
|
| 55:28 | the peak of the action potential in VM is huge. Compared to the |
|
| 55:37 | potential for potassium, potassium has a driving force and potassium channels are |
|
| 55:42 | So who's dominating the game again? . And what is potassium trying to |
|
| 55:47 | is trying to take it home, to take it to its own house |
|
| 55:53 | its own E. K. And almost succeeds. And that's why you |
|
| 55:59 | first of all the um first of , Oh I forgot it's just that |
|
| 56:08 | was I was scrolling through a single presentation and I'm wondering why I can't |
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| 56:14 | because it's a single slide. So have this positive feedback loop driving sodium |
|
| 56:20 | shuts down potassium dominance, tries to it to its own equilibrium potential. |
|
| 56:25 | the pumps here and working against potassium working against concentration gradients for both and |
|
| 56:32 | to restore the member and potential back its resting membrane potential one. So |
|
| 56:40 | is this is in your class lecture and I believe I may have messed |
|
| 56:49 | today by leaving out an interesting, important concept that I also have questions |
|
| 57:00 | And so I think no, it's in here. Mhm. Okay, |
|
| 57:06 | , I'll review my notes but I to talk about the resistance and capacities |
|
| 57:13 | of the membrane because it relates to membrane potential. But it also relates |
|
| 57:18 | active circuits as they're getting engaged during action potential. So, I may |
|
| 57:26 | some 5-10 minutes of next lecture to about what we call membrane equivalent |
|
| 57:32 | And for some of you that are physics or electronics or into computational |
|
| 57:38 | And it's an interesting concept to And it's also the properties of the |
|
| 57:44 | . So membrane has resistance, it allow things through. You have to |
|
| 57:49 | channels, channels have to be There has to be a driving |
|
| 57:53 | Driving force is incorporating everything now because a deliberate potential. Right? And |
|
| 58:01 | electrical forces the VM um and the is a great capacitor. It stores |
|
| 58:13 | capacitors great. If they have a of surface area membrane provides a lot |
|
| 58:21 | surface area capacitor is also great if two plates of the capacitor are very |
|
| 58:26 | to each other so it can That's possible to buy land. |
|
| 58:31 | it has capacities properties that can store charge of the amendment And resistant properties |
|
| 58:37 | it cannot pass the charge really. you need to have the channels that |
|
| 58:41 | open. But put it in six 7. Yeah, Perfect. |
|
| 58:52 | I'm gonna come back to that and gonna force it today. So I |
|
| 58:57 | that the best you know the best diagram for for today. I think |
|
| 59:06 | summarizes everything. I would use this . Now the other thing that is |
|
| 59:13 | in here are two periods and it's off a little bit but there is |
|
| 59:18 | absolute refractory period and the relative refractory . It's also an important concept off |
|
| 59:25 | neurons function and how they function. that once this all a non response |
|
| 59:31 | potential responses initiated, you cannot make sell do any more. And it |
|
| 59:39 | called the absolute refractory period. You make that sell de polarize more. |
|
| 59:45 | if you put more input, make action potential across the equilibrium potential |
|
| 59:50 | You cannot. So only when the starts re polarizing here, you have |
|
| 59:58 | relative refractory period which is not fully in this diagram. It's it's in |
|
| 60:03 | other diagram. And that relative refractory . If you stimulated the south strong |
|
| 60:08 | during this period here you can produce action potential. And this relates to |
|
| 60:14 | we talked about. Remember I said some cells can fire very fast frequencies |
|
| 60:19 | action potentials and others are not so . So that partly depends on the |
|
| 60:26 | the membrane dynamics here in this refractory to themselves may have a longer refractory |
|
| 60:33 | to recover before they produce another action . It's just the kinetics and the |
|
| 60:38 | of the channels that are regulating the and that important messages that all of |
|
| 60:44 | channels sodium channel potassium channel. These players that we're talking about. Their |
|
| 60:53 | educated. So deep polarization is what sodium channel sodium goes in and d |
|
| 61:01 | to sell more and more. Deep opens more sodium channels. Right? |
|
| 61:08 | is leaky. potassium channels are open is dominated by sodium. But then |
|
| 61:14 | have potassium channels in. Okay. so you have a different cycle that |
|
| 61:21 | in here during the re polarization. They're both sodium and potassium are voltage |
|
| 61:29 | channels. So it opens up because a huge driving force is a difference |
|
| 61:35 | in concentration. And you have the regulation by voltage. We are not |
|
| 61:42 | about anything binding to these channels. talked about how robert Mckinnon used the |
|
| 61:48 | channel and he bound things to send toxins to bind. But here we're |
|
| 61:54 | regulating the opening of sodium and potassium by Ligon or chemical. It's all |
|
| 62:00 | dependent of voltage gated channels and their because they actually have gates. And |
|
| 62:14 | and where where am I now voltage will study in the channel kinetics. |
|
| 62:25 | will study in the next lecture So leave three really at least three |
|
| 62:31 | interesting concepts for uh next lecture And will also talk about Tetrodotoxin. And |
|
| 62:43 | will also talk about. What's the on toxin later in this course. |
|
| 62:50 | we'll talk about electro physiological recordings. talk about the kinetics. These are |
|
| 62:57 | channels and the sodium channels have And we'll see what gates. Remember |
|
| 63:02 | told you these polyps chains that form . They're three dimensional structures and they |
|
| 63:06 | these endings that are hanging out and of them service gates. They close |
|
| 63:10 | channel and you actually have to open gates. So the opening of these |
|
| 63:14 | is regulated by voltage. We'll discuss also. And uh we'll talk about |
|
| 63:22 | clamp and we'll talk about the membrane circle. So we'll cover about five |
|
| 63:27 | concepts in the next lecture. And continue talking about action potentials. And |
|
| 63:33 | the concept of back propagation will be last concept before the exam in the |
|
| 63:38 | . So, thank you for being in classroom and on zoom. I |
|
| 63:43 | somehow the chat. Uh Okay. , yes. We founded the action |
|
| 63:50 | . Driving. Awesome. Thank you . I'm gonna disconnect and save the |
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