0:00:01.890,0:00:03.820 So let's talk about[br]pacemaker cells. 0:00:03.820,0:00:07.480 I'm going to actually[br]draw out the action 0:00:07.480,0:00:09.090 potential for a pacemaker cell. 0:00:09.090,0:00:12.620 And remember, this[br]is time over here. 0:00:12.620,0:00:14.990 And let's do it with millivolts. 0:00:14.990,0:00:18.890 This is positive up here[br]and negative down here. 0:00:18.890,0:00:22.770 Now, our pacemaker[br]cells, let's specifically 0:00:22.770,0:00:25.600 talk about the ones[br]in the SA node. 0:00:25.600,0:00:28.000 So this is our SA[br]node action potential, 0:00:28.000,0:00:31.740 and you know it starts out[br]kind of negative and creeps up. 0:00:31.740,0:00:34.170 And that's mainly[br]because of sodium, 0:00:34.170,0:00:36.690 sodium leaking into the cell. 0:00:36.690,0:00:40.970 And other ions are present as[br]well, but that's the major ion. 0:00:40.970,0:00:42.830 Now it gets up to[br]this point, right, 0:00:42.830,0:00:45.200 where I'm drawing[br]kind of a threshold. 0:00:45.200,0:00:46.900 And this threshold is for what? 0:00:46.900,0:00:50.480 Well, this is kind[br]of this dashed line 0:00:50.480,0:00:52.830 represents the point[br]at which calcium 0:00:52.830,0:00:54.530 channels start to open up. 0:00:54.530,0:00:56.600 And so they open up[br]and causes the cell 0:00:56.600,0:00:58.166 to become even more positive. 0:00:58.166,0:00:59.540 So it was already[br]going positive, 0:00:59.540,0:01:01.360 it's going to go[br]even more positive. 0:01:01.360,0:01:03.740 And it's going to get[br]to about that point. 0:01:03.740,0:01:07.680 And then finally, at this[br]point, those calcium channels, 0:01:07.680,0:01:10.230 those voltage gated calcium[br]channels, close down 0:01:10.230,0:01:11.890 and potassium channels open up. 0:01:11.890,0:01:15.810 Which causes the[br]membrane to repolarize. 0:01:15.810,0:01:18.590 So these are the three[br]phases we've talked about. 0:01:18.590,0:01:22.180 This is phase 4, we[br]numbered it as phase 4. 0:01:22.180,0:01:24.750 This is phase 0,[br]and this is phase 1. 0:01:24.750,0:01:28.010 These are the three[br]phases we discussed. 0:01:28.010,0:01:30.010 So now let's think about[br]it a little bit harder. 0:01:30.010,0:01:33.205 Let's say that we[br]view this, and I 0:01:33.205,0:01:35.080 think that's a pretty[br]reasonable thing to do, 0:01:35.080,0:01:37.420 view this as the heartbeat. 0:01:37.420,0:01:39.030 This is one heartbeat, right? 0:01:39.030,0:01:41.817 And you know if we were to[br]keep this picture going, 0:01:41.817,0:01:43.650 basically you would get[br]another one of these 0:01:43.650,0:01:46.275 and another one of these, and it[br]would just basically continue. 0:01:46.275,0:01:48.770 And this is what our heart[br]rate then looks like, right? 0:01:48.770,0:01:51.786 If you were just to look at[br]a strip over, let's say, two, 0:01:51.786,0:01:53.160 three minutes, it[br]would basically 0:01:53.160,0:01:56.870 be just one after another[br]of these kinds of action 0:01:56.870,0:01:59.650 potentials kind of[br]stacked on each other. 0:01:59.650,0:02:02.600 So now if I was to take this[br]heartbeat and shorten it, 0:02:02.600,0:02:05.080 let's say I was to make[br]it instead of ending where 0:02:05.080,0:02:07.780 it does, let's say I[br]ended it right there. 0:02:07.780,0:02:11.140 So that this whole thing kind[br]of gets brought this way. 0:02:11.140,0:02:16.520 Well, it would crunch down on[br]my action potential in phase 4. 0:02:16.520,0:02:18.150 But what would[br]that mean exactly? 0:02:18.150,0:02:20.358 I mean you think, well, so[br]what, so it's a little bit 0:02:20.358,0:02:22.840 more crunched down, happens[br]a little faster, so what? 0:02:22.840,0:02:25.145 Well, what it means,[br]if you think about it, 0:02:25.145,0:02:27.530 is if the heart beats are[br]stacking on top of each other, 0:02:27.530,0:02:30.910 if you make the heartbeat[br]itself a little bit quicker, 0:02:30.910,0:02:34.650 meaning takes less[br]time to finish, 0:02:34.650,0:02:36.700 then the next one can[br]start a little bit early, 0:02:36.700,0:02:38.380 and then that one[br]will finish early, 0:02:38.380,0:02:39.847 and the next one[br]will start early, 0:02:39.847,0:02:41.430 and basically, at[br]the end of a minute, 0:02:41.430,0:02:44.210 you'll have more[br]heartbeats fit in. 0:02:44.210,0:02:47.110 So by having a shorter[br]heartbeat, what you're really 0:02:47.110,0:02:50.010 saying is that you're[br]increasing the heart rate. 0:02:50.010,0:02:53.542 The number of heartbeats[br]in a minute goes up. 0:02:53.542,0:02:55.000 So that's actually[br]pretty powerful. 0:02:55.000,0:02:57.820 Because we think about[br]heart rates all the time, 0:02:57.820,0:02:59.720 but rarely do we think[br]about exactly what 0:02:59.720,0:03:01.840 that means for each[br]individual heartbeat. 0:03:01.840,0:03:04.710 And what it means is that[br]each heartbeat goes quicker. 0:03:04.710,0:03:06.940 Now, the opposite[br]is true too, right? 0:03:06.940,0:03:09.080 You could imagine actually[br]extending this out. 0:03:09.080,0:03:11.760 Let's say the heartbeat actually[br]goes a little bit longer. 0:03:11.760,0:03:13.670 You could extend[br]it out that way. 0:03:13.670,0:03:15.360 And if the heartbeat[br]goes longer, 0:03:15.360,0:03:19.510 then that means that you can get[br]fewer packed into one minute. 0:03:19.510,0:03:21.010 And that means that[br]you're basically 0:03:21.010,0:03:23.840 saying that you're[br]reducing the heart rate. 0:03:23.840,0:03:28.120 So when I say I'm increasing[br]or decreasing the heart rate, 0:03:28.120,0:03:31.890 really what I'm trying to[br]say is that I'm shortening 0:03:31.890,0:03:35.310 or lengthening the heartbeat[br]so that's actually, 0:03:35.310,0:03:37.770 I think, a pretty powerful idea. 0:03:37.770,0:03:39.670 Now let's take it[br]a step further. 0:03:39.670,0:03:42.360 Let's actually do a[br]little thought experiment. 0:03:42.360,0:03:45.760 Let's imagine that this is[br]1/10 of a second right here. 0:03:45.760,0:03:47.780 1/10 of a second. 0:03:47.780,0:03:50.540 And it may not be[br]exactly 1/10 of a second, 0:03:50.540,0:03:52.670 but let's just imagine it is. 0:03:52.670,0:03:56.340 And let's say I wanted to take[br]a look at our cell at this point 0:03:56.340,0:03:59.820 because that's where[br]1/10 of a second has hit. 0:03:59.820,0:04:01.130 What would our cell look like? 0:04:01.130,0:04:04.520 Let me actually just make a[br]little bit of space on a canvas 0:04:04.520,0:04:07.690 and draw out what our cell might[br]look like at 1/10 of a second. 0:04:07.690,0:04:11.920 And just to make sure I keep[br]everyone on the same page, 0:04:11.920,0:04:14.990 this is what's happening[br]in our pacemaker cell 0:04:14.990,0:04:17.070 at 1/10 of a second. 0:04:17.070,0:04:19.180 So at this point,[br]you have a cell. 0:04:19.180,0:04:21.160 Let me actually draw[br]a blown up version 0:04:21.160,0:04:24.680 of our cell that[br]might look like this. 0:04:24.680,0:04:28.100 And this cell is going[br]to have ions flowing in, 0:04:28.100,0:04:30.490 it's going to have, let's[br]say, sodium coming in. 0:04:30.490,0:04:32.845 And we know that this[br]is the dominant ion. 0:04:32.845,0:04:35.960 So let me draw, let's[br]say, a few of them, 0:04:35.960,0:04:39.180 kind of gushing into our cell. 0:04:39.180,0:04:42.172 And we also have some[br]other ions coming in. 0:04:42.172,0:04:43.880 And you might think,[br]well, wait a second, 0:04:43.880,0:04:46.330 I thought only sodium comes in. 0:04:46.330,0:04:48.480 And that's definitely[br]not the case. 0:04:48.480,0:04:50.700 Even though sodium[br]is the dominant ion, 0:04:50.700,0:04:55.510 meaning the cell is mostly[br]permeable to sodium, 0:04:55.510,0:04:59.410 calcium is actually leaking in,[br]and a little bit of potassium 0:04:59.410,0:05:00.560 might be leaking out. 0:05:00.560,0:05:03.830 So you have other ions moving[br]back and forth, as well. 0:05:03.830,0:05:05.710 Even though, in[br]this case, sodium 0:05:05.710,0:05:10.730 is the major contributor[br]to the membrane potential. 0:05:10.730,0:05:14.350 So if that's the case, now[br]let's take another look 0:05:14.350,0:05:16.366 at the membrane. 0:05:16.366,0:05:17.990 Now let's take a look[br]at this membrane, 0:05:17.990,0:05:22.620 and let me show you[br]what might be out here. 0:05:22.620,0:05:25.100 You've got some[br]receptors on this side. 0:05:25.100,0:05:30.800 And those receptors are[br]for a neurotransmitter. 0:05:30.800,0:05:33.490 So there's actually[br]nerves that come down 0:05:33.490,0:05:37.760 and land right on[br]our pacemaker cell. 0:05:37.760,0:05:40.370 And these are the[br]sympathetic nerves. 0:05:43.650,0:05:49.290 And these nerves are releasing[br]some neurotransmitter. 0:05:49.290,0:05:50.960 And this[br]neurotransmitter, I'm just 0:05:50.960,0:05:55.130 going to try to label as[br]I go, is norepinephrine. 0:05:55.130,0:05:56.970 Norepi sometimes it's called. 0:05:59.820,0:06:03.740 So norepinephrine comes and[br]lands on these receptors 0:06:03.740,0:06:06.580 and is going to cause[br]a signal into the cell. 0:06:06.580,0:06:08.850 And it's going to[br]basically tell the cell 0:06:08.850,0:06:11.550 to be permeable to these ions. 0:06:11.550,0:06:15.200 Allow these ions to flow[br]across the membrane. 0:06:15.200,0:06:17.540 So they say, OK, fair enough. 0:06:17.540,0:06:21.255 Now on the other side, you've[br]got another set of receptors. 0:06:21.255,0:06:22.630 And, of course,[br]it's not actually 0:06:22.630,0:06:24.800 divided by one[br]side and the other. 0:06:24.800,0:06:27.290 I'm just doing it[br]to kind of represent 0:06:27.290,0:06:32.050 an idea, which is that[br]on this other receptor, 0:06:32.050,0:06:38.010 you've got other kinds of[br]neurotransmitters landing. 0:06:38.010,0:06:40.850 And these right here,[br]are acetylcholine. 0:06:44.530,0:06:49.230 Now, acetylcholine is also[br]going to send a signal down here 0:06:49.230,0:06:56.100 and this signal is coming[br]from parasympathetic nerves. 0:06:56.100,0:06:58.660 You might have heard of[br]sympathetic and parasympathetic 0:06:58.660,0:06:59.460 nerves. 0:06:59.460,0:07:03.450 These are both part of the[br]autonomic nerve system. 0:07:03.450,0:07:05.010 And the parasympathetic[br]nerves are 0:07:05.010,0:07:06.510 sending kind of an[br]opposite message. 0:07:06.510,0:07:09.330 They're saying to this[br]cell, well, wait a second, 0:07:09.330,0:07:11.810 don't allow so[br]much permeability. 0:07:11.810,0:07:14.850 Don't allow so many ions[br]to go back and forth 0:07:14.850,0:07:17.280 across your membrane. 0:07:17.280,0:07:20.290 So opposite messages[br]coming in, and as it 0:07:20.290,0:07:23.642 turns out, that they kind of[br]balance and offset each other. 0:07:23.642,0:07:25.100 And so you get what[br]I've shown you. 0:07:25.100,0:07:28.210 You get some sodium coming[br]in, a little bit of calcium, 0:07:28.210,0:07:31.160 and a little bit of[br]potassium leaving. 0:07:31.160,0:07:34.610 Now, if I was to actually show[br]you now what could happen. 0:07:34.610,0:07:38.380 Let me try to take a shortcut[br]here and do a little cut, 0:07:38.380,0:07:40.140 paste. 0:07:40.140,0:07:42.410 Imagine that this happens. 0:07:42.410,0:07:43.420 Something like this. 0:07:43.420,0:07:46.990 Let's show you, I'm going to[br]have to move this canvas up 0:07:46.990,0:07:49.080 a little bit. 0:07:49.080,0:07:53.340 But let's say now, you[br]have more sympathetics. 0:07:53.340,0:07:56.030 Let's say you have more[br]sympathetics coming in 0:07:56.030,0:07:59.310 than parasympathetics, then you[br]might get something like this. 0:07:59.310,0:08:02.150 Where instead of just a little[br]bit of neurotransmitters 0:08:02.150,0:08:04.240 here, let's say[br]you get a lot more. 0:08:04.240,0:08:07.390 And let's say now this[br]receptor is also firing, 0:08:07.390,0:08:10.480 and let's say you get[br]a little bit of firing 0:08:10.480,0:08:12.120 from this receptor. 0:08:12.120,0:08:15.940 Well, now you get all three[br]receptors on the left, 0:08:15.940,0:08:19.690 and that really outbalances[br]the one receptor on the right. 0:08:19.690,0:08:21.800 So your sympathetic drive[br]here, you could say, 0:08:21.800,0:08:24.764 is much stronger than your[br]parasympathetic drive. 0:08:24.764,0:08:26.930 And if that's the case, if[br]your sympathetic drive is 0:08:26.930,0:08:29.860 much stronger, than[br]what's going to happen 0:08:29.860,0:08:35.350 is you're going to have more[br]sodium coming into the cell. 0:08:35.350,0:08:37.980 Because, again, the[br]sympathetics are 0:08:37.980,0:08:41.654 trying to get more[br]ion permeability. 0:08:41.654,0:08:45.290 So you have a lot[br]more sodium gushing in 0:08:45.290,0:08:47.870 and you'll get a little[br]bit of extra calcium, too. 0:08:47.870,0:08:50.640 You'll get more[br]calcium here, too. 0:08:50.640,0:08:53.270 And you'll get more[br]potassium leaving the cell. 0:08:53.270,0:08:57.910 So basically sympathetics are[br]going to cause all of the ions 0:08:57.910,0:09:00.630 to increase in the[br]direction of movement. 0:09:00.630,0:09:02.827 So you're going to get[br]more sodium to come in, 0:09:02.827,0:09:04.660 you're going to get[br]more calcium to come in, 0:09:04.660,0:09:07.620 and you're going to get[br]more potassium to leave. 0:09:07.620,0:09:08.560 So that's interesting. 0:09:08.560,0:09:10.719 And let's actually[br]just keep that in mind. 0:09:10.719,0:09:12.510 I'm actually going to[br]do this one more time 0:09:12.510,0:09:14.885 and show you what could happen[br]if the opposite were true. 0:09:14.885,0:09:19.800 Let's say that in this case, you[br]had more parasympathetic drive. 0:09:19.800,0:09:23.835 So let's say here, you have[br]now, in this third scenario-- 0:09:23.835,0:09:26.790 remember the first scenario was[br]kind of the baseline scenario, 0:09:26.790,0:09:28.590 and this third[br]scenario now, let's say 0:09:28.590,0:09:33.390 you have more acetylcholine[br]filling up these receptors. 0:09:33.390,0:09:37.670 And that's outdoing what the[br]sympathetic nerves are doing. 0:09:37.670,0:09:41.240 So now you've got a lot more[br]parasympathetic stimulation. 0:09:41.240,0:09:43.860 Well, now this cell is[br]going to think, OK, well, 0:09:43.860,0:09:47.570 the parasympathetics don't[br]want as much ion movement, 0:09:47.570,0:09:49.840 so less sodium. 0:09:49.840,0:09:51.560 Again, this is all[br]in 1/10 of a second, 0:09:51.560,0:09:54.240 so if you just catch the[br]cell at 1/10 of a second, 0:09:54.240,0:09:55.900 less sodium has moved in. 0:09:55.900,0:09:59.290 Maybe less calcium[br]has gotten in. 0:09:59.290,0:10:02.340 And maybe less[br]potassium has left. 0:10:02.340,0:10:05.080 So if you look at 1/10 of[br]a second, the pictures, 0:10:05.080,0:10:07.680 the snapshots are[br]really, really different. 0:10:07.680,0:10:10.140 So in both scenarios,[br]sympathetics 0:10:10.140,0:10:12.990 and parasympathetics,[br]it's the same ions. 0:10:12.990,0:10:15.110 They're moving in[br]the same direction, 0:10:15.110,0:10:19.050 but what we're looking at[br]is the amount of charge 0:10:19.050,0:10:22.157 that's flowing over[br]a period of time. 0:10:22.157,0:10:24.240 And sometimes you might[br]even use the word current. 0:10:24.240,0:10:25.720 You might say,[br]well, sympathetics 0:10:25.720,0:10:28.870 are increasing the current,[br]and parasympathetics 0:10:28.870,0:10:32.200 are decreasing the current,[br]the amount of charge that's 0:10:32.200,0:10:34.830 moving over a period of time. 0:10:34.830,0:10:37.280 So how would this actually[br]look on our figure? 0:10:37.280,0:10:38.780 So we drew a figure at the top. 0:10:38.780,0:10:40.810 How would this actually[br]look on this figure? 0:10:40.810,0:10:43.470 Well, I'm going to use[br]the colors red and green 0:10:43.470,0:10:47.920 because that's kind of what[br]we've gotten into using here. 0:10:47.920,0:10:51.736 So green, remember that was[br]our sympathetic scenario, well, 0:10:51.736,0:10:53.360 what that's going to[br]do is that's going 0:10:53.360,0:10:59.160 to basically increase the[br]amount of charge rushing in. 0:10:59.160,0:11:03.010 And at 1/10 of a second,[br]you've got more positive ions 0:11:03.010,0:11:04.000 in the cell. 0:11:04.000,0:11:05.730 So, let's say, at[br]that point, you've 0:11:05.730,0:11:07.660 actually already hit threshold. 0:11:07.660,0:11:10.930 And you might now fire[br]in an action potential. 0:11:10.930,0:11:14.200 And it will come[br]down just as before. 0:11:14.200,0:11:17.030 And your heart rate[br]is basically going 0:11:17.030,0:11:21.090 to go up because you've[br]shortened the heartbeat. 0:11:21.090,0:11:23.810 And the opposite's going to[br]happen with parasympathetics. 0:11:23.810,0:11:25.430 So with parasympathetics,[br]you're going 0:11:25.430,0:11:29.840 to have a longer time to[br]get to that threshold. 0:11:29.840,0:11:32.740 Because, again, it's[br]at 1/10 of a second, 0:11:32.740,0:11:35.920 only a little bit of sodium[br]and calcium were inside, 0:11:35.920,0:11:38.310 and only a little bit[br]of potassium had left. 0:11:38.310,0:11:42.230 And you're going to have[br]roughly the same looking 0:11:42.230,0:11:45.530 action potential as before. 0:11:45.530,0:11:48.710 And you've gotten a much[br]lower heart rate now 0:11:48.710,0:11:51.060 because the heartbeat[br]is much longer. 0:11:51.060,0:11:54.390 So you can see that the amount[br]of current that's flowing 0:11:54.390,0:11:55.170 is changing. 0:11:55.170,0:11:58.855 And so, really, we're tweaking[br]phase 4 with our sympathetics 0:11:58.855,0:12:02.580 and parasympathetics to[br]change our heart rate.