1 00:00:00,090 --> 00:00:02,490 The following content is provided under a Creative 2 00:00:02,490 --> 00:00:04,059 Commons license. 3 00:00:04,059 --> 00:00:06,330 Your support will help MIT OpenCourseWare 4 00:00:06,330 --> 00:00:10,720 continue to offer high quality educational resources for free. 5 00:00:10,720 --> 00:00:13,320 To make a donation or view additional materials 6 00:00:13,320 --> 00:00:17,280 from hundreds of MIT courses, visit MIT OpenCourseWare 7 00:00:17,280 --> 00:00:18,450 at ocw.mit.edu. 8 00:00:26,200 --> 00:00:28,750 HAZEL SIVE: All right, let's look at some of your questions. 9 00:00:34,100 --> 00:00:35,600 A bunch of them are-- you know what, 10 00:00:35,600 --> 00:00:38,630 I'm probably going to use that screen most of the time. 11 00:00:38,630 --> 00:00:40,050 Because this one's not fitting. 12 00:00:40,050 --> 00:00:42,920 But let's look on this screen. 13 00:00:42,920 --> 00:00:48,200 Your questions really focused around IPS cells and the kind 14 00:00:48,200 --> 00:00:51,770 of magic of IPS cells. 15 00:00:51,770 --> 00:00:54,650 And there were a couple of major questions that came up. 16 00:00:57,380 --> 00:01:00,599 What's the problem with using IPS cells therapeutically? 17 00:01:00,599 --> 00:01:01,640 Well, there are a number. 18 00:01:01,640 --> 00:01:03,500 One, they're so new that really we 19 00:01:03,500 --> 00:01:10,190 don't know what kinds of cell types these IPS cells can make, 20 00:01:10,190 --> 00:01:13,250 so it's not clear how to use them. 21 00:01:13,250 --> 00:01:15,470 Another problem actually, which my colleague, 22 00:01:15,470 --> 00:01:18,560 Professor Jaenisch works on is the question 23 00:01:18,560 --> 00:01:20,885 of how to actually grow these cells. 24 00:01:24,010 --> 00:01:25,990 I have a voice issue this morning. 25 00:01:25,990 --> 00:01:30,430 So you know, the quieter you are, the more you'll 26 00:01:30,430 --> 00:01:34,180 be able to hear my words. 27 00:01:34,180 --> 00:01:38,609 IPS cells, human cells, grow very slowly in the laboratory. 28 00:01:38,609 --> 00:01:40,150 And it's very difficult to grow them. 29 00:01:40,150 --> 00:01:43,090 So there are some basic questions in biology, 30 00:01:43,090 --> 00:01:46,510 as to how to grow these cells to enough numbers that 31 00:01:46,510 --> 00:01:48,190 would actually be useful. 32 00:01:48,190 --> 00:01:50,260 But here's another one that's very important. 33 00:01:50,260 --> 00:01:51,910 The transcription factors that we 34 00:01:51,910 --> 00:01:55,450 use to convert adult cells into IPS cells 35 00:01:55,450 --> 00:01:58,690 included an oncogene called c-Myc. 36 00:01:58,690 --> 00:02:02,680 And Myc is the kind of gene you don't want floating 37 00:02:02,680 --> 00:02:05,890 around your body nice and active in your cells, 38 00:02:05,890 --> 00:02:07,840 because it will give you cancer. 39 00:02:07,840 --> 00:02:11,410 So the challenge is how to actually use 40 00:02:11,410 --> 00:02:13,900 Myc and other potent transcription 41 00:02:13,900 --> 00:02:18,220 factors to turn adult cells into stem cells 42 00:02:18,220 --> 00:02:21,640 but not have the stem cells give the recipient cancer. 43 00:02:21,640 --> 00:02:23,260 And there's some very clever ways 44 00:02:23,260 --> 00:02:25,510 that people are trying to get around this. 45 00:02:32,730 --> 00:02:35,520 It is really impossible to teach you, 46 00:02:35,520 --> 00:02:36,980 if there are groups of you talking. 47 00:02:39,640 --> 00:02:41,030 I just cannot do it. 48 00:02:41,030 --> 00:02:45,590 So those of you talking, please don't. 49 00:02:45,590 --> 00:02:47,370 Thank you. 50 00:02:47,370 --> 00:02:50,940 All right, so what's the big deal about IPS cells? 51 00:02:50,940 --> 00:02:54,540 Well, the big deal is they can be your own. 52 00:02:54,540 --> 00:02:57,720 In theory-- and maybe in practice, a decade, 53 00:02:57,720 --> 00:03:00,390 five years maybe from now-- 54 00:03:00,390 --> 00:03:04,170 your own cells, your skin cells could be removed from you, 55 00:03:04,170 --> 00:03:06,270 could be dealt with in the laboratory, 56 00:03:06,270 --> 00:03:09,180 turned into your own stem cells, and put back 57 00:03:09,180 --> 00:03:11,350 into your own body, and they'd be your own. 58 00:03:11,350 --> 00:03:14,670 So of course, they wouldn't be rejected by you. 59 00:03:14,670 --> 00:03:16,270 And that is an enormous deal. 60 00:03:16,270 --> 00:03:19,240 They're called autologous cells. 61 00:03:19,240 --> 00:03:20,770 There's an ethical issue, in that 62 00:03:20,770 --> 00:03:26,380 you don't have to harvest any embryos to get stem cell lines. 63 00:03:26,380 --> 00:03:28,240 And that's a big deal. 64 00:03:28,240 --> 00:03:31,690 And here's a conceptual deal. 65 00:03:31,690 --> 00:03:33,310 When we talked about development, 66 00:03:33,310 --> 00:03:36,430 we talked about this directional pathway, 67 00:03:36,430 --> 00:03:38,650 where uncommitted cells became committed 68 00:03:38,650 --> 00:03:40,660 became differentiated. 69 00:03:40,660 --> 00:03:45,170 It was really thought that that was a one-way pathway. 70 00:03:45,170 --> 00:03:48,840 But what IPS cell technology has shown-- 71 00:03:48,840 --> 00:03:51,780 let's look at this-- 72 00:03:51,780 --> 00:03:55,250 all right, we can get the idea from one of these two screens. 73 00:03:55,250 --> 00:03:57,440 What IPS cell technology has shown 74 00:03:57,440 --> 00:03:59,390 is that you can reverse differentiation. 75 00:03:59,390 --> 00:04:01,940 You can take differentiated adult cells 76 00:04:01,940 --> 00:04:04,040 and with the right regulatory factors, 77 00:04:04,040 --> 00:04:07,340 you can turn them into stem cells. 78 00:04:07,340 --> 00:04:10,610 And so conceptually, that's a big deal. 79 00:04:10,610 --> 00:04:13,400 Very good, great questions. 80 00:04:13,400 --> 00:04:16,380 My next office hours are on Monday, 12-1. 81 00:04:16,380 --> 00:04:19,760 Come along or email me. 82 00:04:19,760 --> 00:04:22,220 But now we're going to turn to a new module, 83 00:04:22,220 --> 00:04:24,300 and that is the nervous system. 84 00:04:24,300 --> 00:04:27,640 And this is where we are in the course. 85 00:04:27,640 --> 00:04:29,800 You've done all the foundational material. 86 00:04:29,800 --> 00:04:31,660 We've talked about formation. 87 00:04:31,660 --> 00:04:33,850 And now we're going to talk about systems 88 00:04:33,850 --> 00:04:36,530 and the nervous system in particular. 89 00:04:36,530 --> 00:04:41,375 Let's start with the question of what a system is. 90 00:04:47,070 --> 00:04:49,440 Building up, the complexity of what 91 00:04:49,440 --> 00:04:51,490 we're talking about in life. 92 00:04:51,490 --> 00:04:55,020 A system refers to many organs that work together 93 00:04:55,020 --> 00:04:56,195 with one common function. 94 00:05:08,410 --> 00:05:13,400 Many organs working together with one overall function. 95 00:05:13,400 --> 00:05:15,400 And you will talk about two in the course. 96 00:05:15,400 --> 00:05:18,670 You'll talk about the nervous system and the immune system 97 00:05:18,670 --> 00:05:20,380 with Professor Jacks. 98 00:05:20,380 --> 00:05:23,200 The nervous system, which is the topic of the next three 99 00:05:23,200 --> 00:05:26,320 lectures, has to do with communication-- 100 00:05:26,320 --> 00:05:30,460 has to do with communication from the outside to the inside 101 00:05:30,460 --> 00:05:34,450 of an animal's body, has to do with communication within 102 00:05:34,450 --> 00:05:38,360 the body, and has to do with communication to get 103 00:05:38,360 --> 00:05:41,920 the organism-- the animal, because plants don't have 104 00:05:41,920 --> 00:05:43,120 nervous system-- 105 00:05:43,120 --> 00:05:45,130 the animal to do something. 106 00:05:45,130 --> 00:06:01,030 So the nervous system is about communication 107 00:06:01,030 --> 00:06:10,010 to or from or within the body of an animal. 108 00:06:13,770 --> 00:06:17,110 We've had a number of electrical analogies in the course. 109 00:06:17,110 --> 00:06:19,510 You will remember the famous signaling analogy 110 00:06:19,510 --> 00:06:22,960 of turning on the light switch over there on the wall. 111 00:06:22,960 --> 00:06:26,330 But now we move on to another electrical analogy, 112 00:06:26,330 --> 00:06:28,570 which is actually a truer one. 113 00:06:28,570 --> 00:06:31,780 And I'm going to use the analogy for the nervous system 114 00:06:31,780 --> 00:06:35,170 of talking about wires that transmit 115 00:06:35,170 --> 00:06:38,200 the signal, by which cells communicates. 116 00:06:38,200 --> 00:06:41,140 I'm going to talk about connectors between the wires. 117 00:06:41,140 --> 00:06:42,910 And then I'm going to talk about circuits. 118 00:06:42,910 --> 00:06:45,160 And those are going to be the topics of the next three 119 00:06:45,160 --> 00:06:45,860 lectures. 120 00:06:45,860 --> 00:06:54,655 So wires, connectors, and circuits. 121 00:06:58,710 --> 00:07:01,760 And those will be nervous system 1 to 3, 122 00:07:01,760 --> 00:07:03,960 the lectures in this module. 123 00:07:03,960 --> 00:07:06,015 Today, we're going to talk about the wires. 124 00:07:12,900 --> 00:07:14,410 And there will be three topics. 125 00:07:14,410 --> 00:07:17,670 The first is the cell type that's 126 00:07:17,670 --> 00:07:21,880 got something to do with the wiring for this communication. 127 00:07:21,880 --> 00:07:25,450 The second is something called the action potential, 128 00:07:25,450 --> 00:07:27,210 which is the signal by which cells 129 00:07:27,210 --> 00:07:31,150 communicate within themselves. 130 00:07:31,150 --> 00:07:35,770 And the third has to do with the ion channels and pumps. 131 00:07:43,860 --> 00:07:46,110 But let's start by phrasing the problem 132 00:07:46,110 --> 00:07:49,730 in a kind of a cool way. 133 00:07:49,730 --> 00:07:52,370 If you look in the human-- 134 00:07:52,370 --> 00:07:53,780 let's look on this screen. 135 00:07:53,780 --> 00:07:57,230 If you look in the human, and you outline the nerves. 136 00:07:57,230 --> 00:08:00,530 And if you went to see the living, plasticized 137 00:08:00,530 --> 00:08:04,480 human exhibits, you would have seen the plasticized nerves. 138 00:08:04,480 --> 00:08:06,020 They're really extraordinary. 139 00:08:06,020 --> 00:08:09,740 The network of nerves, which are the unit of communication 140 00:08:09,740 --> 00:08:10,940 throughout the body. 141 00:08:10,940 --> 00:08:12,320 Is enormous. 142 00:08:12,320 --> 00:08:19,090 And it embraces every single part of the body, almost. 143 00:08:19,090 --> 00:08:21,280 The cell that's involved in communication-- 144 00:08:21,280 --> 00:08:23,980 we'll draw this out in a moment-- is the neuron. 145 00:08:23,980 --> 00:08:25,810 And one of the things about neurons 146 00:08:25,810 --> 00:08:29,560 is that they've got very long processes, called axons, 147 00:08:29,560 --> 00:08:32,600 that we will deal with in depth today. 148 00:08:32,600 --> 00:08:36,549 But let's phrase things more intuitively. 149 00:08:36,549 --> 00:08:39,309 This is what our brains look like. 150 00:08:39,309 --> 00:08:42,480 They in fact do not have nerves innovating them. 151 00:08:42,480 --> 00:08:45,120 And so if you actually have brain surgery, 152 00:08:45,120 --> 00:08:47,260 you can really be awake during surgery. 153 00:08:47,260 --> 00:08:50,590 Because there are no nerves within the brain, or at least 154 00:08:50,590 --> 00:08:52,630 no pain receptors within the brain. 155 00:08:52,630 --> 00:08:54,910 Of course, the brain has nerves, but there are 156 00:08:54,910 --> 00:08:57,700 no pain receptors in the brain. 157 00:08:57,700 --> 00:08:59,920 Human brain. 158 00:08:59,920 --> 00:09:03,640 Billions and billions and trillions of neurons. 159 00:09:03,640 --> 00:09:05,920 We'll talk about numbers in future lectures. 160 00:09:05,920 --> 00:09:10,130 But let's look a little more deeply in the brain, 161 00:09:10,130 --> 00:09:13,330 so you can see how packed it is with neurons 162 00:09:13,330 --> 00:09:15,760 and how the connections between the neurons 163 00:09:15,760 --> 00:09:18,820 are so unbelievably complex that thinking 164 00:09:18,820 --> 00:09:22,720 about how you use circuitry to construct 165 00:09:22,720 --> 00:09:24,070 the human nervous system-- 166 00:09:24,070 --> 00:09:26,350 or indeed that of most animals-- 167 00:09:26,350 --> 00:09:28,720 is an enormous problem. 168 00:09:28,720 --> 00:09:31,480 Professor Sebastian Seung here-- 169 00:09:31,480 --> 00:09:34,520 whose name is off the screen, and I apologize to him, 170 00:09:34,520 --> 00:09:37,990 it's the screen snafu, it will be on your power points 171 00:09:37,990 --> 00:09:42,370 when you download these from the web-- 172 00:09:42,370 --> 00:09:45,580 is working on the task of putting together 173 00:09:45,580 --> 00:09:48,700 all the connections in the human brain. 174 00:09:48,700 --> 00:09:51,190 And starting with a little cube of brain-- 175 00:09:51,190 --> 00:09:53,990 this is about 100 microns, it's not quite a cube, 176 00:09:53,990 --> 00:09:58,340 but it's approximately a 100-micron cube-- 177 00:09:58,340 --> 00:10:01,140 he's worked to try to figure out what all the cell 178 00:10:01,140 --> 00:10:04,440 connections are and what all the cells are, 179 00:10:04,440 --> 00:10:07,320 within this little tiny cube of brain, 180 00:10:07,320 --> 00:10:12,780 which is just a tiny, tiny fraction of your brain. 181 00:10:12,780 --> 00:10:14,430 So look at this. 182 00:10:14,430 --> 00:10:18,080 This is an electron micrograph that he's 183 00:10:18,080 --> 00:10:20,060 put a bunch of electron micrographs 184 00:10:20,060 --> 00:10:23,060 together, to build this 3D structure. 185 00:10:23,060 --> 00:10:25,790 And now his students and those of Professor Lichtman 186 00:10:25,790 --> 00:10:30,320 at Harvard go and outline a particular cell 187 00:10:30,320 --> 00:10:33,020 in serial sections, through this cube. 188 00:10:33,020 --> 00:10:34,680 These are very tiny sections. 189 00:10:34,680 --> 00:10:37,700 These are about five nanometer sections. 190 00:10:37,700 --> 00:10:40,250 And then they put these sections together. 191 00:10:40,250 --> 00:10:42,170 And you can get the three dimensional 192 00:10:42,170 --> 00:10:46,640 structure of the neuron, as it's going through the cube. 193 00:10:46,640 --> 00:10:50,450 And you can start to map how this neuron lies next 194 00:10:50,450 --> 00:10:52,990 to other neurons. 195 00:10:52,990 --> 00:10:56,940 OK, there it's going backwards. 196 00:10:56,940 --> 00:10:59,370 And there are two cells lying next to one another 197 00:10:59,370 --> 00:11:02,100 that you can get in 3D rendering, 198 00:11:02,100 --> 00:11:05,820 with this very painstaking process of first, 199 00:11:05,820 --> 00:11:08,550 getting sections of the brain, putting them 200 00:11:08,550 --> 00:11:12,180 all together into a chunk, and then deconstructing 201 00:11:12,180 --> 00:11:15,390 the individual cells shapes within that chunk. 202 00:11:15,390 --> 00:11:18,310 If you do that for the whole chunk of tissue, 203 00:11:18,310 --> 00:11:19,230 this is what you get. 204 00:11:19,230 --> 00:11:21,180 There's that red and that green neuron. 205 00:11:21,180 --> 00:11:24,090 Here is a blue one, there's a yellow one, lime, 206 00:11:24,090 --> 00:11:30,062 purple, red, dark blue, yellow, orange. 207 00:11:30,062 --> 00:11:30,645 It's daunting. 208 00:11:33,820 --> 00:11:34,810 There you go. 209 00:11:34,810 --> 00:11:38,350 In that tiny little chunk of brain, 210 00:11:38,350 --> 00:11:41,050 that is how packed the cells are. 211 00:11:41,050 --> 00:11:43,840 And the connections between them are enormous. 212 00:11:43,840 --> 00:11:48,010 And that is just less than a millionth of your brain. 213 00:11:48,010 --> 00:11:50,980 So to figure out all the connections, 214 00:11:50,980 --> 00:11:54,260 all the circuitry in the nervous system, is an enormous task. 215 00:11:54,260 --> 00:11:55,690 And we don't know it. 216 00:11:55,690 --> 00:11:57,940 We'll talk about what we do know later on. 217 00:11:57,940 --> 00:12:00,850 But I wanted to frame the problem for you, 218 00:12:00,850 --> 00:12:04,900 so that you have a sense of where we're trying to go. 219 00:12:04,900 --> 00:12:06,510 Let's go back to the neuron. 220 00:12:09,820 --> 00:12:13,420 And let's talk about cell type and how 221 00:12:13,420 --> 00:12:18,880 cell type is important for thinking about signaling 222 00:12:18,880 --> 00:12:21,290 in the nervous system. 223 00:12:21,290 --> 00:12:23,530 So like everything else in the body, 224 00:12:23,530 --> 00:12:28,330 communication uses cells as its currency. 225 00:12:28,330 --> 00:12:32,500 And the cell type is the special kind 226 00:12:32,500 --> 00:12:35,800 of cell type, which is the neuron. 227 00:12:40,450 --> 00:12:53,380 So neurons are the connecting/wiring cells. 228 00:12:53,380 --> 00:12:56,140 There's a second type of cell in the nervous system that 229 00:12:56,140 --> 00:12:59,350 is really pivotal for nervous system function that 230 00:12:59,350 --> 00:13:02,020 are called glia. 231 00:13:02,020 --> 00:13:06,820 And these are cells which are referred to as support cells. 232 00:13:06,820 --> 00:13:08,230 But that's not really fair. 233 00:13:08,230 --> 00:13:11,980 They guide neurons, and as we'll mention later, 234 00:13:11,980 --> 00:13:15,130 they also insulate neurons, so that the wires 235 00:13:15,130 --> 00:13:17,150 don't short circuit. 236 00:13:17,150 --> 00:13:18,945 So they guide and insulate neurons. 237 00:13:23,700 --> 00:13:27,630 The structure of the neuron is important to understand 238 00:13:27,630 --> 00:13:28,920 its function. 239 00:13:28,920 --> 00:13:37,120 Like all cells, it's got a nucleus and cytoplasm. 240 00:13:37,120 --> 00:13:40,880 And here it is, the nucleus, the cytoplasm. 241 00:13:40,880 --> 00:13:44,380 And this region of the neuron is called the cell body. 242 00:13:48,340 --> 00:13:53,280 But unlike other cells, coming out from this cell body 243 00:13:53,280 --> 00:13:54,570 there are processes. 244 00:13:54,570 --> 00:13:57,180 And they are very substantial processes. 245 00:13:57,180 --> 00:14:02,970 On one side of the cell body are usually fairly short processes. 246 00:14:02,970 --> 00:14:06,360 They can be branched, and there can be bunches of them. 247 00:14:06,360 --> 00:14:08,100 And these are called dendrites. 248 00:14:18,300 --> 00:14:23,010 Dendrites are processes that receive a signal. 249 00:14:23,010 --> 00:14:26,830 So they are the place where there is a signaling-- 250 00:14:26,830 --> 00:14:28,450 let me get rid of that dendrite-- 251 00:14:28,450 --> 00:14:29,915 there is a signaling input. 252 00:14:33,930 --> 00:14:37,010 The signal that dendrites receive moves 253 00:14:37,010 --> 00:14:41,430 through the cell body and into another process, which 254 00:14:41,430 --> 00:14:46,150 is called the axon and is very long. 255 00:14:46,150 --> 00:14:49,290 And the fact that it is very long 256 00:14:49,290 --> 00:14:52,860 is actually what this lecture is all about. 257 00:14:52,860 --> 00:14:55,440 So the axon is the wire. 258 00:14:55,440 --> 00:14:59,370 Axons can be up to a meter long. 259 00:14:59,370 --> 00:15:00,420 Here's the axon. 260 00:15:10,530 --> 00:15:14,040 And there are axons that start in your spinal cord 261 00:15:14,040 --> 00:15:19,230 and move all the way down your leg, from a single cell. 262 00:15:19,230 --> 00:15:21,490 We'll talk about why that is in a moment. 263 00:15:21,490 --> 00:15:26,130 These axons branch at their ends. 264 00:15:26,130 --> 00:15:29,940 And they connect to another neuron or something else, 265 00:15:29,940 --> 00:15:32,260 but we'll draw another neuron. 266 00:15:32,260 --> 00:15:41,040 Here's another neuron with its dendrites and another axon. 267 00:15:41,040 --> 00:15:49,020 The connection-- here is neuron 1 and neuron 2. 268 00:15:53,220 --> 00:15:56,980 And the connection between axons and dendrites-- 269 00:15:56,980 --> 00:16:00,040 or as you'll discover, axons in the cell body-- 270 00:16:00,040 --> 00:16:02,440 is called a synapse. 271 00:16:02,440 --> 00:16:05,860 Some people say synapse-- 272 00:16:05,860 --> 00:16:09,620 that's the connection-- either is OK. 273 00:16:13,400 --> 00:16:17,860 And the thing is that this input that 274 00:16:17,860 --> 00:16:21,520 is way over on the left hand side of the board 275 00:16:21,520 --> 00:16:33,240 is transmitted, along the axon, into the next neuron, 276 00:16:33,240 --> 00:16:37,710 and then along the next neuron. 277 00:16:37,710 --> 00:16:39,825 This is the signal. 278 00:16:43,660 --> 00:16:46,690 And we have to think about why cells 279 00:16:46,690 --> 00:16:49,870 might want to have these very long processes to do this, 280 00:16:49,870 --> 00:16:51,730 and then how the signal is transmitted. 281 00:16:54,570 --> 00:16:58,900 The reason that cells have got these long processes rather 282 00:16:58,900 --> 00:16:59,400 than-- 283 00:16:59,400 --> 00:17:01,440 well, let's actually step back a moment. 284 00:17:01,440 --> 00:17:03,210 Let's think about how cells might 285 00:17:03,210 --> 00:17:05,290 communicate with one another. 286 00:17:05,290 --> 00:17:08,099 You could imagine a whole bunch of little round cells, 287 00:17:08,099 --> 00:17:11,700 all lined up, so that there a meter of them 288 00:17:11,700 --> 00:17:15,660 that go from your spinal cord down to your leg. 289 00:17:15,660 --> 00:17:18,030 And that would give you a chain of communication 290 00:17:18,030 --> 00:17:19,710 from your spinal cord to your leg. 291 00:17:19,710 --> 00:17:22,109 And you could have one back to your brain and so on. 292 00:17:22,109 --> 00:17:24,980 And that in theory would work OK. 293 00:17:24,980 --> 00:17:29,510 But it turns out that cell-cell communication is very slow, 294 00:17:29,510 --> 00:17:31,310 and that cells have figured out a way 295 00:17:31,310 --> 00:17:36,020 to transmit a signal along their own length that is very rapid. 296 00:17:36,020 --> 00:17:39,050 You know that there is a finite time between getting 297 00:17:39,050 --> 00:17:40,940 a stimulus and a response. 298 00:17:40,940 --> 00:17:42,860 You know, you touch something hot, 299 00:17:42,860 --> 00:17:45,770 you can tell it actually takes a moment before you figure out 300 00:17:45,770 --> 00:17:46,640 it's hot. 301 00:17:46,640 --> 00:17:49,400 That's the speed of transmission of the signal, up 302 00:17:49,400 --> 00:17:50,540 into your brain. 303 00:17:50,540 --> 00:17:53,780 And you say, wow, that's hot, move my finger. 304 00:17:53,780 --> 00:17:57,840 If you had cells that were connecting rather than long 305 00:17:57,840 --> 00:18:01,820 processes of one cell, it would take you that much longer 306 00:18:01,820 --> 00:18:04,340 to actually make that-- maybe 10 times longer-- 307 00:18:04,340 --> 00:18:05,780 to make that connection. 308 00:18:05,780 --> 00:18:07,640 And you'd get a bad burned finger. 309 00:18:10,760 --> 00:18:15,080 So the axon is the thing that allows rapid transmission 310 00:18:15,080 --> 00:18:15,665 of the signal. 311 00:18:24,140 --> 00:18:25,400 So the axon is long. 312 00:18:28,000 --> 00:18:31,660 It leads to an intracellular signal. 313 00:18:37,640 --> 00:18:45,220 And this is very rapid, relative to an intercellular signal. 314 00:18:58,030 --> 00:19:02,950 But how do you transmit a signal along a cell? 315 00:19:02,950 --> 00:19:07,320 Well, axons do this by using movement of ions. 316 00:19:15,630 --> 00:19:21,300 So the signal along the axon is due to movement of ions. 317 00:19:21,300 --> 00:19:27,720 And this is called an action potential, as we will discuss. 318 00:19:33,150 --> 00:19:36,720 And this process draws on a property of all cells 319 00:19:36,720 --> 00:19:39,240 that neurons have capitalized on. 320 00:19:39,240 --> 00:19:43,320 So almost all cells have got a potential difference 321 00:19:43,320 --> 00:19:46,530 across their membrane, because there is a charge difference 322 00:19:46,530 --> 00:19:47,885 across the plasma membrane. 323 00:19:52,890 --> 00:19:56,480 So almost all cells have what is called 324 00:19:56,480 --> 00:20:01,490 a membrane potential, which is a membrane potential difference. 325 00:20:08,350 --> 00:20:13,210 And in general, cells are more positive outside than they 326 00:20:13,210 --> 00:20:14,620 are inside. 327 00:20:14,620 --> 00:20:15,805 So outside the cell-- 328 00:20:18,840 --> 00:20:21,470 and this is worth your remembering-- 329 00:20:21,470 --> 00:20:23,960 it is more positive. 330 00:20:23,960 --> 00:20:27,100 And it's more positive because there's a lot of sodium ion. 331 00:20:29,680 --> 00:20:31,360 You'll see the why this is important. 332 00:20:31,360 --> 00:20:36,700 There's low potassium ion, and there's some high chloride ion. 333 00:20:36,700 --> 00:20:39,190 But really, the thing that's important 334 00:20:39,190 --> 00:20:46,350 is that there's very high sodium concentration outside the cell. 335 00:20:46,350 --> 00:20:51,525 Conversely, inside the cell is obviously more negative. 336 00:20:56,760 --> 00:20:57,735 Sodium is low. 337 00:21:01,270 --> 00:21:06,820 Potassium is higher but still not very high. 338 00:21:06,820 --> 00:21:10,720 And there's a bunch of ions that are kind of trapped 339 00:21:10,720 --> 00:21:11,230 in the cell. 340 00:21:14,500 --> 00:21:17,630 Why is this important? 341 00:21:17,630 --> 00:21:19,090 Let me see what I have next here. 342 00:21:19,090 --> 00:21:21,700 OK, most cells show a potential difference. 343 00:21:21,700 --> 00:21:22,420 Here it is. 344 00:21:22,420 --> 00:21:24,310 Here is written the potential difference. 345 00:21:24,310 --> 00:21:26,590 Neurons are somewhere between minus 70 346 00:21:26,590 --> 00:21:28,750 and minus 60 millivolts, where you 347 00:21:28,750 --> 00:21:31,870 are talking about the relative potential difference 348 00:21:31,870 --> 00:21:34,570 inside to outside, that's why it's negative. 349 00:21:34,570 --> 00:21:36,940 And you can see tumor cells actually 350 00:21:36,940 --> 00:21:39,640 have got a very low membrane potential, which may or may not 351 00:21:39,640 --> 00:21:40,580 be significant. 352 00:21:48,790 --> 00:21:54,580 What is the nature of the signal that neurons 353 00:21:54,580 --> 00:22:02,560 use to transmit from the input, along the axon, 354 00:22:02,560 --> 00:22:04,510 to the next cell? 355 00:22:04,510 --> 00:22:07,420 Particularly, what is the signal that's 356 00:22:07,420 --> 00:22:10,330 transmitted along the axon? 357 00:22:10,330 --> 00:22:15,440 And the answer is something called an action potential. 358 00:22:15,440 --> 00:22:26,760 It's the signal transmitted along the axon, the wire 359 00:22:26,760 --> 00:22:29,290 that I referred to. 360 00:22:29,290 --> 00:22:38,190 And an accident potential, which I'm going to abbreviate as AP, 361 00:22:38,190 --> 00:22:39,030 will define-- 362 00:22:39,030 --> 00:22:40,980 and you'll understand this in a moment-- 363 00:22:40,980 --> 00:22:43,810 as a local, transient depolarization. 364 00:22:50,010 --> 00:22:53,410 Local, transient-- just lasts a moment-- 365 00:22:53,410 --> 00:22:57,430 depolarization, change in membrane potential. 366 00:23:00,494 --> 00:23:02,410 And I'm going to do most of this on the board. 367 00:23:02,410 --> 00:23:03,826 You have a hand-out, but I'm going 368 00:23:03,826 --> 00:23:06,490 to do most of this on the board because it works better 369 00:23:06,490 --> 00:23:09,100 as a conversation than a demonstration. 370 00:23:09,100 --> 00:23:11,630 Let's draw a a bit of an axon. 371 00:23:11,630 --> 00:23:13,730 Here is the axon. 372 00:23:13,730 --> 00:23:22,330 Two plasma membranes-- outside, inside, outside. 373 00:23:22,330 --> 00:23:23,345 So this is the axon. 374 00:23:27,490 --> 00:23:30,920 Plasma membrane, PM. 375 00:23:30,920 --> 00:23:32,820 And what we are going to do-- 376 00:23:32,820 --> 00:23:35,690 and here is a cytoplasm-- 377 00:23:35,690 --> 00:23:39,250 what we are going to do is take a chunk of the axon 378 00:23:39,250 --> 00:23:43,180 and blow it up and focus on just one plasma membrane, 379 00:23:43,180 --> 00:23:47,290 on one side of the axon, and look and see in detail 380 00:23:47,290 --> 00:23:48,620 what is going on there. 381 00:23:48,620 --> 00:23:52,840 So let's take this chunk and blow it up, 382 00:23:52,840 --> 00:23:58,420 so that we now have the plasma membrane--and you remember 383 00:23:58,420 --> 00:23:59,690 it's a lipid bilayer. 384 00:23:59,690 --> 00:24:01,480 But I'm drawing it as a single line, 385 00:24:01,480 --> 00:24:02,910 because it's really a pain control 386 00:24:02,910 --> 00:24:04,390 to draw it as a lipid bilayer. 387 00:24:04,390 --> 00:24:08,710 But you know it's a lipid bilayer. 388 00:24:08,710 --> 00:24:11,980 On one side-- and here is outside the cell 389 00:24:11,980 --> 00:24:14,200 and inside the cell. 390 00:24:14,200 --> 00:24:19,190 On one side, there are lots of positive charges. 391 00:24:19,190 --> 00:24:23,670 And on the other side, there are fewer and relatively more 392 00:24:23,670 --> 00:24:24,450 negative charges. 393 00:24:27,760 --> 00:24:31,420 When the axon looks like this, with this balance 394 00:24:31,420 --> 00:24:33,610 of positive and negative charges, 395 00:24:33,610 --> 00:24:36,790 it's said to be at resting potential. 396 00:24:39,500 --> 00:24:45,255 And resting potential is about minus 60 millivolts. 397 00:24:48,910 --> 00:24:52,650 OK, what's our goal? 398 00:24:52,650 --> 00:25:07,470 Our goal is to start here, at this asterisk, 399 00:25:07,470 --> 00:25:10,590 and to transmit a signal along the length 400 00:25:10,590 --> 00:25:15,150 of this piece of axon and to transmit the signal 401 00:25:15,150 --> 00:25:18,300 in a directional way. 402 00:25:18,300 --> 00:25:23,160 So our goal is to transmit a directional signal. 403 00:25:39,170 --> 00:25:42,140 Let's draw three time points, each of which 404 00:25:42,140 --> 00:25:47,630 have a plasma membrane of this particular segment of axon. 405 00:25:47,630 --> 00:25:49,490 And let us-- 406 00:25:49,490 --> 00:25:53,180 I'm going to move over a bit, to this side of the board-- 407 00:25:53,180 --> 00:26:01,400 let's have them here, here, and here. 408 00:26:01,400 --> 00:26:05,420 And so we're going to have a time vector going diagonally 409 00:26:05,420 --> 00:26:07,550 across the board. 410 00:26:07,550 --> 00:26:12,650 And we started off with something 411 00:26:12,650 --> 00:26:16,140 that looked like it did on the board 412 00:26:16,140 --> 00:26:19,020 above at resting potential. 413 00:26:19,020 --> 00:26:23,400 And now, we're going to-- over a very short segment of membrane, 414 00:26:23,400 --> 00:26:25,380 we're going to reverse the membrane charge, 415 00:26:25,380 --> 00:26:27,300 or the cell's going to do it. 416 00:26:27,300 --> 00:26:29,820 So that on the outside now, there's 417 00:26:29,820 --> 00:26:33,240 a little part of the membrane that's 418 00:26:33,240 --> 00:26:36,630 negative outside and positive inside. 419 00:26:36,630 --> 00:26:42,870 And the rest is positive outside and negative inside. 420 00:26:42,870 --> 00:26:57,240 Over time, this is called a depolarization, a reversal 421 00:26:57,240 --> 00:26:59,510 of the membrane potential. 422 00:26:59,510 --> 00:27:05,500 Over time, that depolarization, that initial depolarization 423 00:27:05,500 --> 00:27:06,760 is going to rectify. 424 00:27:06,760 --> 00:27:09,400 It's going to go back to how it was. 425 00:27:09,400 --> 00:27:13,360 So you'll get positive charges outside again. 426 00:27:13,360 --> 00:27:18,720 But the segment of membrane next door is going to depolarize, 427 00:27:18,720 --> 00:27:23,520 so it now becomes negative outside and positive inside. 428 00:27:23,520 --> 00:27:29,660 And the rest is positive outside and negative inside. 429 00:27:29,660 --> 00:27:33,200 That little piece of membrane, the second-- 430 00:27:33,200 --> 00:27:40,970 so that's depolarization 1, here's depolarization 2. 431 00:27:40,970 --> 00:27:45,860 Again, over time, you're going to get rectification 432 00:27:45,860 --> 00:27:49,340 of that second depolarization. 433 00:27:49,340 --> 00:27:51,560 And you've got the idea now, it's 434 00:27:51,560 --> 00:27:55,890 going to move further down the axon. 435 00:27:55,890 --> 00:28:01,280 So here is depolarization 3. 436 00:28:01,280 --> 00:28:07,920 And you recall that this is outside and inside the axon. 437 00:28:07,920 --> 00:28:09,720 So if you look at my diagram-- 438 00:28:09,720 --> 00:28:11,480 I haven't given you any mechanism-- 439 00:28:11,480 --> 00:28:15,980 but you can see here we have got a signal that 440 00:28:15,980 --> 00:28:23,110 is moving in this direction, along the axon. 441 00:28:23,110 --> 00:28:26,360 Each of these depolarizations that I've drawn 442 00:28:26,360 --> 00:28:28,300 is called an action potential. 443 00:28:38,900 --> 00:28:42,800 And I'll give you, in a moment, some more properties, 444 00:28:42,800 --> 00:28:46,310 so that you'll know an action potential when you see one. 445 00:28:46,310 --> 00:28:48,680 But there are a couple of questions that arise 446 00:28:48,680 --> 00:28:51,410 from this easy-to-draw diagram. 447 00:28:51,410 --> 00:28:53,330 Firstly, how does this really happen? 448 00:28:53,330 --> 00:28:56,930 How do charges reverse across the membrane? 449 00:28:56,930 --> 00:29:00,440 Secondly, why is the signal unidirectional? 450 00:29:00,440 --> 00:29:02,450 Why doesn't it go backwards? 451 00:29:02,450 --> 00:29:06,110 And thirdly, how do you reset the depolarization 452 00:29:06,110 --> 00:29:07,131 once it's happened? 453 00:29:07,131 --> 00:29:08,630 And all of these things you will see 454 00:29:08,630 --> 00:29:12,230 are connected, but let's raise these questions. 455 00:29:12,230 --> 00:29:13,415 So how does this happen? 456 00:29:16,710 --> 00:29:18,300 Why is it unidirectional? 457 00:29:25,630 --> 00:29:27,770 And what does it mean-- 458 00:29:27,770 --> 00:29:32,950 or what is the mechanism of resetting 459 00:29:32,950 --> 00:29:36,940 the membrane potential, after a depolarization has happened? 460 00:29:36,940 --> 00:29:44,530 As for example here, you have reset the membrane potential. 461 00:29:51,460 --> 00:29:55,240 So the answer to all of this is complex. 462 00:29:55,240 --> 00:30:00,320 And we'll answer it in chunks, as we tend to do in this class. 463 00:30:00,320 --> 00:30:03,290 And the first thing we'll answer with respect to 464 00:30:03,290 --> 00:30:05,230 is changing membrane potential. 465 00:30:10,590 --> 00:30:17,390 Let's start off again with our axon chunk, with outside 466 00:30:17,390 --> 00:30:24,200 and inside, and the charge distribution 467 00:30:24,200 --> 00:30:26,900 that is at resting potential. 468 00:30:32,250 --> 00:30:34,880 And along comes some kind of input. 469 00:30:34,880 --> 00:30:37,700 It might be touch, it might be another neuron 470 00:30:37,700 --> 00:30:39,620 touching a second neuron. 471 00:30:39,620 --> 00:30:42,800 It might be vision, light, that comes along, 472 00:30:42,800 --> 00:30:45,390 some kind of input. 473 00:30:45,390 --> 00:30:47,610 Here it is. 474 00:30:47,610 --> 00:30:52,590 And this input acts on a very local part of the membrane. 475 00:30:52,590 --> 00:30:54,700 And it changes the membrane potential 476 00:30:54,700 --> 00:31:00,240 just a tiny bit, such that the membrane potential might 477 00:31:00,240 --> 00:31:04,090 reach something called threshold potential. 478 00:31:04,090 --> 00:31:07,230 So let's look, let's draw it out. 479 00:31:07,230 --> 00:31:09,840 Here it is. 480 00:31:09,840 --> 00:31:13,420 Just over a one little tiny bit of the membrane, 481 00:31:13,420 --> 00:31:15,310 there's some kind of charge reversal. 482 00:31:15,310 --> 00:31:18,775 The positive charges come from outside, and they move inside. 483 00:31:26,430 --> 00:31:30,750 And we'll call this potential difference threshold potential. 484 00:31:33,910 --> 00:31:37,620 And if you want a number, it's about minus 55 millivolts. 485 00:31:40,530 --> 00:31:42,970 What happens after threshold? 486 00:31:42,970 --> 00:31:46,140 Well threshold, you understand what threshold is. 487 00:31:46,140 --> 00:31:48,990 It means something happens because you have 488 00:31:48,990 --> 00:31:51,490 reached a point of no return. 489 00:31:51,490 --> 00:31:55,440 And what happens is that there is now an action potential, 490 00:31:55,440 --> 00:31:58,830 and there is a massive movement of the positive sodium 491 00:31:58,830 --> 00:32:01,300 ions into the cell. 492 00:32:01,300 --> 00:32:04,140 So from threshold potential there 493 00:32:04,140 --> 00:32:22,360 is a massive movement, again out and in. 494 00:32:26,010 --> 00:32:29,720 So now you've got instead of this little tiny region 495 00:32:29,720 --> 00:32:34,670 of depolarization, you've got a large region of depolarization. 496 00:32:34,670 --> 00:32:38,150 So this is a small, depol-- 497 00:32:38,150 --> 00:32:43,790 for depolarization-- leading to a very large depolarization 498 00:32:43,790 --> 00:32:47,830 of the kind that I drew on the board before. 499 00:32:47,830 --> 00:32:52,270 This large depolarization is called the action potential. 500 00:33:02,290 --> 00:33:04,630 And it has several properties. 501 00:33:04,630 --> 00:33:07,540 The action potential reverses the membrane potential 502 00:33:07,540 --> 00:33:08,620 almost completely. 503 00:33:08,620 --> 00:33:11,800 So now in this region of the membrane, 504 00:33:11,800 --> 00:33:16,870 it's at about plus 60 millivolts. 505 00:33:16,870 --> 00:33:18,640 So it's a massive depolarization. 506 00:33:18,640 --> 00:33:22,150 You completely reverse the ion distribution 507 00:33:22,150 --> 00:33:26,170 over a small region of the membrane. 508 00:33:26,170 --> 00:33:29,080 It's very local, however. 509 00:33:29,080 --> 00:33:33,480 An action potential occurs over-- 510 00:33:33,480 --> 00:33:37,470 or this massive depolarization occurs over 511 00:33:37,470 --> 00:33:40,590 about a micron of membrane. 512 00:33:40,590 --> 00:33:43,980 It takes one to two milliseconds to set up. 513 00:33:43,980 --> 00:33:48,420 It involves the movement of about 10 to the 5th ions, 514 00:33:48,420 --> 00:33:49,710 from the outside in. 515 00:33:52,860 --> 00:33:54,930 And I've told you the potential. 516 00:33:54,930 --> 00:33:57,480 The other thing that is really critical 517 00:33:57,480 --> 00:34:01,560 that you have to understand is something called all or none. 518 00:34:08,260 --> 00:34:11,409 The depolarization you get with an action potential 519 00:34:11,409 --> 00:34:13,929 is either complete, or it doesn't happen. 520 00:34:13,929 --> 00:34:17,530 If you reach threshold, you reverse polarity, 521 00:34:17,530 --> 00:34:21,310 and you get this complete depolarization to plus 60 522 00:34:21,310 --> 00:34:23,650 millivolts from minus 60. 523 00:34:23,650 --> 00:34:26,080 You do not get a partial depolarization 524 00:34:26,080 --> 00:34:32,440 to plus 10 or 20 or 30 sometimes, or 35. 525 00:34:32,440 --> 00:34:36,460 For a given neuron, you get a specific action potential. 526 00:34:36,460 --> 00:34:40,030 And it either happens, or it doesn't happen. 527 00:34:40,030 --> 00:34:45,179 So all on none, very important. 528 00:34:45,179 --> 00:34:50,429 No little or big action potentials. 529 00:34:50,429 --> 00:34:54,230 And now we've got a depolarization, 530 00:34:54,230 --> 00:34:56,929 but we haven't answered two questions. 531 00:34:56,929 --> 00:35:00,380 We haven't answered the question of unidirection, 532 00:35:00,380 --> 00:35:02,840 and we haven't answered the question of resetting. 533 00:35:02,840 --> 00:35:05,480 So let's do that on the next board. 534 00:35:05,480 --> 00:35:09,140 And let's start off, actually, with an action potential. 535 00:35:11,970 --> 00:35:16,320 And I'm actually going to draw an action potential, kind 536 00:35:16,320 --> 00:35:19,395 of in the middle of this axon. 537 00:35:28,020 --> 00:35:30,170 You'll see why. 538 00:35:30,170 --> 00:35:32,720 When you get an action potential, what's happening 539 00:35:32,720 --> 00:35:36,230 is that sodium ions are moving from the outside inside. 540 00:35:36,230 --> 00:35:38,660 And those sodium ions-- because they're just ions-- 541 00:35:38,660 --> 00:35:41,720 will start to diffuse in the cytoplasm. 542 00:35:41,720 --> 00:35:44,690 And as they diffuse next door, they'll 543 00:35:44,690 --> 00:35:46,850 change the membrane potential, which 544 00:35:46,850 --> 00:35:49,640 will reach threshold, which will trigger 545 00:35:49,640 --> 00:35:54,230 an action potential in the membrane chunk next door. 546 00:35:54,230 --> 00:35:56,900 And then those ions will diffuse, 547 00:35:56,900 --> 00:35:59,600 to make the chunk of membrane next door 548 00:35:59,600 --> 00:36:02,060 reach threshold potential. 549 00:36:02,060 --> 00:36:05,926 And you'll get an action potential triggered, and so on. 550 00:36:05,926 --> 00:36:08,050 But the ions, of course, because they're just ions, 551 00:36:08,050 --> 00:36:09,560 can move in either direction. 552 00:36:09,560 --> 00:36:11,690 So the ions can move back. 553 00:36:11,690 --> 00:36:14,470 If this is where your action potential took place, 554 00:36:14,470 --> 00:36:16,660 the ions could move in that direction 555 00:36:16,660 --> 00:36:20,120 and trigger an action potential going back, up the axon, 556 00:36:20,120 --> 00:36:21,700 towards the cell body. 557 00:36:21,700 --> 00:36:23,360 Why doesn't that happen? 558 00:36:23,360 --> 00:36:25,990 It doesn't happen because once you've 559 00:36:25,990 --> 00:36:29,200 triggered an action potential, that membrane becomes 560 00:36:29,200 --> 00:36:32,740 refractory, unable to trigger another action 561 00:36:32,740 --> 00:36:34,690 potential for a while. 562 00:36:34,690 --> 00:36:37,270 And during that time where the membrane 563 00:36:37,270 --> 00:36:40,660 is unable to respond and make another action potential, 564 00:36:40,660 --> 00:36:44,410 the ions have diffused away and gone on down the axon. 565 00:36:44,410 --> 00:36:47,980 And so you get a unidirectional propagation. 566 00:36:47,980 --> 00:36:49,220 Let's try to draw that out. 567 00:36:49,220 --> 00:36:50,950 So here's an action potential. 568 00:36:55,510 --> 00:37:04,525 And the ions that are moving in will diffuse. 569 00:37:07,820 --> 00:37:13,240 And they will take the membrane next door to threshold. 570 00:37:21,510 --> 00:37:35,230 And so they'll trigger an action potential next door. 571 00:37:39,680 --> 00:37:43,130 Those ions fusing backwards can't do anything. 572 00:37:43,130 --> 00:37:46,880 Because once the membrane has had an action potential, 573 00:37:46,880 --> 00:37:49,160 it can't have another one for a while. 574 00:37:49,160 --> 00:37:57,580 So this membrane here, next door to the action potential, 575 00:37:57,580 --> 00:38:08,460 is refractory to depolarization-- 576 00:38:15,470 --> 00:38:18,020 that is a really horrendous spelling 577 00:38:18,020 --> 00:38:19,790 job there, depolarization-- 578 00:38:22,340 --> 00:38:24,590 for some period of time. 579 00:38:24,590 --> 00:38:29,470 Let's say for about a second or a little less than that, 580 00:38:29,470 --> 00:38:31,790 but somewhere around there. 581 00:38:31,790 --> 00:38:34,310 And so that means that the action potential 582 00:38:34,310 --> 00:38:35,540 is unidirectional. 583 00:38:35,540 --> 00:38:38,130 The ions can diffuse in both directions, 584 00:38:38,130 --> 00:38:40,970 but the action potential can only go in one. 585 00:38:40,970 --> 00:38:45,395 So that gives you a direction of your signal. 586 00:38:47,990 --> 00:38:51,170 And also, I have cavalierly drawn on there 587 00:38:51,170 --> 00:38:54,980 that the membrane potential reverses and resets itself, 588 00:38:54,980 --> 00:38:57,920 where the action potential previously occurred. 589 00:38:57,920 --> 00:39:00,180 And we'll talk about that more in a moment. 590 00:39:00,180 --> 00:39:02,930 So here, the membrane potential has reset. 591 00:39:11,770 --> 00:39:16,762 So this is a theoretical walk through action potentials. 592 00:39:16,762 --> 00:39:18,220 And I gave you a bunch of handouts. 593 00:39:18,220 --> 00:39:21,220 But I'm not going to go through them, because you can use them 594 00:39:21,220 --> 00:39:23,800 as a test or as an exercise after class, 595 00:39:23,800 --> 00:39:26,410 to see how much you understood. 596 00:39:26,410 --> 00:39:29,680 One of the things about conductance along an axon 597 00:39:29,680 --> 00:39:31,510 is that it's very quick. 598 00:39:31,510 --> 00:39:36,070 It takes a very short time from touching that hot thing 599 00:39:36,070 --> 00:39:38,500 to realizing you've touched it. 600 00:39:38,500 --> 00:39:41,020 But one of the reasons it's so short 601 00:39:41,020 --> 00:39:44,770 is because you're not sending an action potential all the way 602 00:39:44,770 --> 00:39:47,110 along an axon like we're drawing. 603 00:39:47,110 --> 00:39:49,600 You don't really get successive parts 604 00:39:49,600 --> 00:39:51,880 of the membrane depolarizing. 605 00:39:51,880 --> 00:39:54,160 Because that actually, although it's faster 606 00:39:54,160 --> 00:39:58,160 than intercellular connections, is still quite slow. 607 00:39:58,160 --> 00:40:00,580 So there's a way that a cell insulates itself, 608 00:40:00,580 --> 00:40:04,450 an axon insulates itself, to give you action potentials 609 00:40:04,450 --> 00:40:07,060 just to particular places. 610 00:40:07,060 --> 00:40:11,590 And that really speeds up the rate of transmission 611 00:40:11,590 --> 00:40:13,360 of an action potential. 612 00:40:13,360 --> 00:40:15,550 And I've got that on the slide here, 613 00:40:15,550 --> 00:40:17,290 and we're right on the board. 614 00:40:17,290 --> 00:40:27,820 So that during depolarization and after 615 00:40:27,820 --> 00:40:33,310 and all the time, ions leak from the axon. 616 00:40:40,450 --> 00:40:46,090 And this decreases the frequency of action potential formation. 617 00:40:49,480 --> 00:40:54,250 And so what cells do, it's kind of like a short-- 618 00:40:54,250 --> 00:40:55,870 no, it's not quite short circuiting, 619 00:40:55,870 --> 00:40:58,330 but it's a bad electrical wire. 620 00:40:58,330 --> 00:41:09,070 And so what the cell has done is to insulate itself 621 00:41:09,070 --> 00:41:11,290 with layers of fatty cells. 622 00:41:11,290 --> 00:41:14,470 And these cells are really kind of amazing. 623 00:41:14,470 --> 00:41:16,900 Most of the cells that insulates the neurons 624 00:41:16,900 --> 00:41:20,990 in the nervous system wrap around the neurons, 625 00:41:20,990 --> 00:41:22,670 as in this diagram. 626 00:41:22,670 --> 00:41:24,490 You can see here is a cell. 627 00:41:24,490 --> 00:41:28,330 And these lines are because a single cell has wrapped itself 628 00:41:28,330 --> 00:41:29,650 around the neuron. 629 00:41:29,650 --> 00:41:32,140 You know that the plasma membrane is lipid. 630 00:41:32,140 --> 00:41:34,540 It doesn't conduct ions, and so you've 631 00:41:34,540 --> 00:41:37,420 got really a fatty layer of insulation. 632 00:41:41,830 --> 00:41:46,240 And the thing that insulates the cells is something 633 00:41:46,240 --> 00:41:51,520 called a myelin sheath, which is lipid plus some protein. 634 00:41:51,520 --> 00:41:56,080 But it's a really hydrophobic layer 635 00:41:56,080 --> 00:41:59,080 that wraps around the neurons and insulates them. 636 00:41:59,080 --> 00:42:01,300 Along the neurons that are insulated, 637 00:42:01,300 --> 00:42:04,540 there are specific places where there is no insulation. 638 00:42:04,540 --> 00:42:07,540 And that's where action potentials take place. 639 00:42:07,540 --> 00:42:22,545 So action potentials take place at nods without myelin. 640 00:42:29,150 --> 00:42:32,660 And this is one way that neurons really speed up 641 00:42:32,660 --> 00:42:34,700 their conductance rate. 642 00:42:34,700 --> 00:42:37,490 And so I put here action potential frequency, 643 00:42:37,490 --> 00:42:38,960 but actually that's not correct. 644 00:42:42,930 --> 00:42:47,130 I'm going to talk about rate of transmission. 645 00:42:53,980 --> 00:42:56,200 So how does this all go together? 646 00:42:56,200 --> 00:43:04,180 Let's look at a movie, where here's the neuron, and here 647 00:43:04,180 --> 00:43:07,550 is the axon, transmitting an action potential 648 00:43:07,550 --> 00:43:09,470 along its length. 649 00:43:09,470 --> 00:43:13,310 And here's a different way of depicting the action potential, 650 00:43:13,310 --> 00:43:16,320 as a graph of voltage against time. 651 00:43:16,320 --> 00:43:19,930 And that's something that you'll practice in section. 652 00:43:19,930 --> 00:43:21,680 But what I want you to see is that there's 653 00:43:21,680 --> 00:43:24,020 an action potential moving along the axon. 654 00:43:26,880 --> 00:43:30,540 And the axon can transmit many, many action potentials, 655 00:43:30,540 --> 00:43:33,330 one after the other, with a short recovery 656 00:43:33,330 --> 00:43:34,410 period in between. 657 00:43:43,830 --> 00:43:48,240 We still have not answered quite the question 658 00:43:48,240 --> 00:43:50,950 of how action potentials work. 659 00:43:50,950 --> 00:43:56,750 And the answer to that is to consider ion channels 660 00:43:56,750 --> 00:44:09,230 and pumps, because all of this charge distribution 661 00:44:09,230 --> 00:44:10,550 doesn't just happen. 662 00:44:10,550 --> 00:44:12,950 It's set up by the cell, and it's 663 00:44:12,950 --> 00:44:18,650 set up by ion channels and pumps, which we can write 664 00:44:18,650 --> 00:44:22,910 Regulate Membrane Potential. 665 00:44:22,910 --> 00:44:26,255 Let's review very briefly what ion channels and pumps are. 666 00:44:26,255 --> 00:44:28,310 We've talked about them a bunch. 667 00:44:28,310 --> 00:44:30,140 But you need to know some essences 668 00:44:30,140 --> 00:44:32,390 for this particular module. 669 00:44:32,390 --> 00:44:36,830 Ion channels allow ions across the membrane by diffusion. 670 00:44:42,690 --> 00:44:44,960 So here is an ion channel. 671 00:44:44,960 --> 00:44:47,720 And I'm drawing a channel which is open. 672 00:44:51,520 --> 00:44:58,430 And the ions move by diffusion, across the channel. 673 00:44:58,430 --> 00:45:02,820 But there are other classes of ion channels, 674 00:45:02,820 --> 00:45:04,790 which are not always open. 675 00:45:04,790 --> 00:45:06,326 They are called gated. 676 00:45:06,326 --> 00:45:07,700 And we talked about them, when we 677 00:45:07,700 --> 00:45:10,870 talked about protein secretion, protein localization. 678 00:45:16,720 --> 00:45:26,070 So gated channels under a particular stimulus 679 00:45:26,070 --> 00:45:33,200 can be closed and then change to the open confirmation, 680 00:45:33,200 --> 00:45:37,780 after they've been given the appropriate stimulus. 681 00:45:37,780 --> 00:45:41,200 So here there is some kind of stimulus. 682 00:45:43,870 --> 00:45:47,960 And a channel that is gated will open. 683 00:45:47,960 --> 00:45:51,620 A third kind of way of getting ions across the membrane 684 00:45:51,620 --> 00:45:57,280 is to use a pump, where a pump is localized in the plasma 685 00:45:57,280 --> 00:46:00,800 membrane as well. 686 00:46:00,800 --> 00:46:03,770 But instead of a diffusion-governed process 687 00:46:03,770 --> 00:46:06,740 to get ions across the membrane, the pump 688 00:46:06,740 --> 00:46:09,990 is actively moving ions across the membrane. 689 00:46:09,990 --> 00:46:15,150 So ion pumps actively transport ions. 690 00:46:22,040 --> 00:46:27,010 And they generally require energy, ATP, in order to do so. 691 00:46:27,010 --> 00:46:29,500 And all of these things are essential to set 692 00:46:29,500 --> 00:46:32,500 the membrane potential and to change it during action 693 00:46:32,500 --> 00:46:35,050 potential formation. 694 00:46:35,050 --> 00:46:37,101 If we consider the resting potential-- actually, 695 00:46:37,101 --> 00:46:38,850 let me see what I have on the slides here. 696 00:46:44,950 --> 00:46:46,570 This is a really cool thing. 697 00:46:46,570 --> 00:46:49,720 All right, let me get through our board work, 698 00:46:49,720 --> 00:46:59,260 and then we'll do what is really cool after or on Monday. 699 00:47:01,950 --> 00:47:05,880 In order to set up the resting potential, 700 00:47:05,880 --> 00:47:09,030 there are several kinds of channels and pumps 701 00:47:09,030 --> 00:47:11,320 that you need to be aware of. 702 00:47:11,320 --> 00:47:14,940 One of them-- which is a biggie and for which a Nobel Prize was 703 00:47:14,940 --> 00:47:16,900 given some decades ago-- 704 00:47:16,900 --> 00:47:19,110 is called the sodium potassium pump. 705 00:47:22,830 --> 00:47:25,200 And this is really a big thing. 706 00:47:25,200 --> 00:47:29,480 It's also called the sodium potassium ATPase. 707 00:47:29,480 --> 00:47:36,020 And what it does is to pump three sodium ions out 708 00:47:36,020 --> 00:47:42,120 of the cell and put two potassium ions into the cell. 709 00:47:42,120 --> 00:47:45,620 And this is an enormously important pump for life. 710 00:47:45,620 --> 00:47:48,560 And you can see what it does is to increase the sodium 711 00:47:48,560 --> 00:47:52,220 concentration outside the cell and increase the potassium 712 00:47:52,220 --> 00:47:55,490 concentration inside. 713 00:47:55,490 --> 00:48:01,990 There is also something called an open potassium channel that 714 00:48:01,990 --> 00:48:04,270 will allow all this potassium that's 715 00:48:04,270 --> 00:48:07,600 being pumped in by the sodium potassium pump 716 00:48:07,600 --> 00:48:10,700 to start diffusing out of the cell. 717 00:48:10,700 --> 00:48:12,850 But in actual fact, it doesn't all diffuse out. 718 00:48:12,850 --> 00:48:16,300 Because it hits the positive charges of the sodium 719 00:48:16,300 --> 00:48:20,030 ions on the outside, and there's an electrostatic repulsion. 720 00:48:20,030 --> 00:48:23,750 And so that limits how much potassium-- 721 00:48:23,750 --> 00:48:27,460 by Monday, I will either be able to speak by Monday 722 00:48:27,460 --> 00:48:29,190 or I will have completely lost my voice. 723 00:48:32,140 --> 00:48:34,630 You'll have the option. 724 00:48:34,630 --> 00:48:39,760 So the open potassium channel allows potassium out 725 00:48:39,760 --> 00:48:49,060 by diffusion, until it is repelled or stopped 726 00:48:49,060 --> 00:48:52,750 by electrostatic forces coming from the sodium ions. 727 00:49:03,180 --> 00:49:05,000 And then a third ion that's open, 728 00:49:05,000 --> 00:49:10,050 an ion channel that's open is the chloride channel, which 729 00:49:10,050 --> 00:49:11,536 we won't discuss right now. 730 00:49:17,500 --> 00:49:19,450 During the action potential, there 731 00:49:19,450 --> 00:49:22,180 is an enormously important ion channel 732 00:49:22,180 --> 00:49:25,270 that is the last thing I'll mention today. 733 00:49:25,270 --> 00:49:28,150 And that's called the voltage gated sodium channel. 734 00:49:44,910 --> 00:49:49,200 This is an ion channel that, like many ion channels, 735 00:49:49,200 --> 00:49:52,420 consists of a complex of proteins. 736 00:49:52,420 --> 00:49:55,690 We'll make a note of that, I'll make a note of that next time. 737 00:49:55,690 --> 00:49:58,140 But the voltage gated sodium channel 738 00:49:58,140 --> 00:50:01,570 is sensitive to membrane potential. 739 00:50:01,570 --> 00:50:04,500 And when threshold potential is reached, 740 00:50:04,500 --> 00:50:06,780 there is a change in the confirmation 741 00:50:06,780 --> 00:50:16,150 of this channel, which is closed normally at resting content 742 00:50:16,150 --> 00:50:23,540 but becomes open at threshold potential, 743 00:50:23,540 --> 00:50:28,790 to lead to the action potential. 744 00:50:28,790 --> 00:50:32,840 And it becomes open through actually the sliding 745 00:50:32,840 --> 00:50:35,630 of one of the alpha helices that make up 746 00:50:35,630 --> 00:50:38,090 the proteins of the channel. 747 00:50:38,090 --> 00:50:40,870 And the sliding alpha helices slide 748 00:50:40,870 --> 00:50:44,570 because their charges change, the charges of the amino acids 749 00:50:44,570 --> 00:50:45,500 change. 750 00:50:45,500 --> 00:50:47,330 And that opens up the channel. 751 00:50:47,330 --> 00:50:50,120 So I'm going to show you one picture 752 00:50:50,120 --> 00:50:53,310 of the last of the sodium channel, 753 00:50:53,310 --> 00:50:54,950 the voltage gated sodium channel. 754 00:50:58,590 --> 00:50:59,204 Here it is. 755 00:50:59,204 --> 00:51:00,120 And then we'll finish. 756 00:51:00,120 --> 00:51:03,350 Take a look at this quickly. 757 00:51:03,350 --> 00:51:07,620 Here is the voltage gated sodium channel closed. 758 00:51:07,620 --> 00:51:10,500 Amino acids blocking up the pore. 759 00:51:10,500 --> 00:51:13,800 And there it opens up, to let the ions in. 760 00:51:13,800 --> 00:51:16,530 And we'll finish this on Monday.