0:00:00.750,0:00:04.480 We know from the last video that[br]if we have a high calcium 0:00:04.480,0:00:09.040 ion concentration inside of the[br]muscle cell, those calcium 0:00:09.040,0:00:13.500 ions will bond to the troponin[br]proteins which will then 0:00:13.500,0:00:17.140 change their shape in such a way[br]that the tropomyosin will 0:00:17.140,0:00:20.580 be moved out of the way and so[br]then the myosin heads can 0:00:20.580,0:00:23.310 crawl along the actin filaments[br]and them we'll 0:00:23.310,0:00:24.950 actually have muscle[br]contractions. 0:00:24.950,0:00:29.140 So high calcium concentration,[br]or calcium ion concentration, 0:00:29.140,0:00:30.850 we have contraction. 0:00:30.850,0:00:35.560 Low calcium ion concentration,[br]these troponin proteins go to 0:00:35.560,0:00:39.060 their standard confirmation and[br]they pull-- or you can say 0:00:39.060,0:00:42.600 they move the tropomyosin back[br]in the way of the myosin 0:00:42.600,0:00:44.165 heads-- and we have[br]no contraction. 0:00:53.750,0:00:57.140 So the next obvious question[br]is, how does the muscle 0:00:57.140,0:00:59.850 regulate whether we have high[br]calcium concentration and 0:00:59.850,0:01:03.350 contraction or low calcium[br]concentration and relaxation? 0:01:03.350,0:01:04.940 Or even a better question[br]is, how does the 0:01:04.940,0:01:05.830 nervous system do it? 0:01:05.830,0:01:09.490 How does the nervous system tell[br]the muscle to contract, 0:01:09.490,0:01:11.550 to make its calcium[br]concentration high and 0:01:11.550,0:01:14.010 contract or to make it[br]low again and relax? 0:01:14.010,0:01:17.900 And to understand that, let's[br]do a little bit a review of 0:01:17.900,0:01:20.790 what we learned on the[br]videos on neurons. 0:01:20.790,0:01:24.000 Let me draw the terminal[br]junction of 0:01:24.000,0:01:27.500 an axon right here. 0:01:27.500,0:01:30.540 Instead of having a synapse[br]with a dendrite of another 0:01:30.540,0:01:32.890 neuron, it's going to have[br]a synapse with an 0:01:32.890,0:01:35.130 actual muscle cell. 0:01:35.130,0:01:37.145 So this is its synapse with[br]the actual muscle cell. 0:01:44.420,0:01:47.170 This is a synapse with an[br]actual muscle cell. 0:01:47.170,0:01:50.070 Let me label everything just[br]so you don't get confused. 0:01:50.070,0:01:51.470 This is the axon. 0:01:51.470,0:01:53.470 We could call it the terminal[br]end of an axon. 0:01:57.610,0:01:58.860 This is the synapse. 0:02:05.440,0:02:08.150 Just a little terminology from[br]the neuron videos-- this space 0:02:08.150,0:02:10.210 was a synaptic cleft. 0:02:10.210,0:02:13.650 This is the presynaptic[br]neuron. 0:02:13.650,0:02:15.430 This is-- I guess you could[br]kind of view it-- the 0:02:15.430,0:02:16.830 post-synaptic cell. 0:02:16.830,0:02:19.050 It's not a neuron[br]in this case. 0:02:19.050,0:02:21.090 And then just so we[br]have-- this is our 0:02:21.090,0:02:30.240 membrane of muscle cell. 0:02:30.240,0:02:32.540 And I'm going to do-- probably[br]the next video or maybe a 0:02:32.540,0:02:34.530 video after that, I'll actually[br]show you the anatomy 0:02:34.530,0:02:35.610 of a muscle cell. 0:02:35.610,0:02:37.230 In this, it'll be a little[br]abstract because we really 0:02:37.230,0:02:39.300 want to understand how[br]the calcium ion 0:02:39.300,0:02:42.810 concentration is regulated. 0:02:42.810,0:02:44.060 This is called a sarcolemma. 0:02:53.580,0:02:56.120 So this is the membrane[br]of the muscle cell. 0:02:56.120,0:02:59.070 And this right here-- you could[br]imagine it's just a fold 0:02:59.070,0:03:00.980 into the membrane of[br]the muscle cell. 0:03:00.980,0:03:04.000 If I were to look at the surface[br]of the muscle cell, 0:03:04.000,0:03:05.850 then it would look like a little[br]bit of a hole or an 0:03:05.850,0:03:09.040 indentation that goes into the[br]cell, but here we did a cross 0:03:09.040,0:03:14.000 section so you can imagine it[br]folding in, but if you poked 0:03:14.000,0:03:16.590 it in with a needle or[br]something, this is 0:03:16.590,0:03:17.240 what you would get. 0:03:17.240,0:03:19.100 You would get a fold[br]in the membrane. 0:03:19.100,0:03:20.460 And this right here is[br]called a T-tubule. 0:03:26.360,0:03:28.100 And the T just stands[br]for transverse. 0:03:28.100,0:03:31.720 It's going transverse to the[br]surface of the membrane. 0:03:31.720,0:03:35.060 And over here-- and this is the[br]really important thing in 0:03:35.060,0:03:36.560 this video, or the[br]really important 0:03:36.560,0:03:37.520 organelle in this video. 0:03:37.520,0:03:42.410 You have this organelle inside[br]of the muscle cell called the 0:03:42.410,0:03:43.890 sarcoplasmic reticulum. 0:03:54.740,0:03:57.700 And it actually is very similar[br]to an endoplasmic 0:03:57.700,0:04:03.180 reticulum in somewhat of what[br]it is or maybe how it's 0:04:03.180,0:04:06.750 related to an endoplasmic[br]reiticulum-- but here its main 0:04:06.750,0:04:07.760 function is storage. 0:04:07.760,0:04:10.400 While an endoplasmic reticulum,[br]it's involved in 0:04:10.400,0:04:14.470 protein development and it has[br]ribosomes attached to it, but 0:04:14.470,0:04:18.860 this is purely a storage[br]organelle. 0:04:18.860,0:04:22.500 What the sarcoplasmic reticulum[br]does it has calcium 0:04:22.500,0:04:32.920 ion pumps on its membrane and[br]what these do is they're ATP 0:04:32.920,0:04:37.530 ases, which means that they[br]use ATP to fuel the pump. 0:04:37.530,0:04:42.450 So you have ATP come in, ATP[br]attaches to it, and maybe a 0:04:42.450,0:04:52.620 calcium ion will attach to it,[br]and when the ATP hydrolyzes 0:04:52.620,0:05:01.470 into ADP plus a phosphate[br]group, that changes the 0:05:01.470,0:05:04.140 confirmation of this protein[br]and it pumps 0:05:04.140,0:05:05.700 the calcium ion in. 0:05:05.700,0:05:08.230 So the calcium ions[br]get pumped in. 0:05:08.230,0:05:12.610 So the net effect of all of[br]these calcium ion pumps on the 0:05:12.610,0:05:16.540 membrane of the sarcoplasmic[br]reticulum is in a resting 0:05:16.540,0:05:20.700 muscle, we'll have a very high[br]concentration of calcium ions 0:05:20.700,0:05:21.950 on the inside. 0:05:26.630,0:05:28.570 Now, I think you could[br]probably guess 0:05:28.570,0:05:29.980 where this is going. 0:05:29.980,0:05:33.010 When the muscle needs to[br]contract, these calcium ions 0:05:33.010,0:05:37.320 get dumped out into the[br]cytoplasm of the cell. 0:05:37.320,0:05:42.610 And then they're able to bond[br]to the troponin right here, 0:05:42.610,0:05:45.120 and do everything we talked[br]about in the last video. 0:05:45.120,0:05:49.180 So what we care about is, just[br]how does it know when to dump 0:05:49.180,0:05:51.760 its calcium ions into the[br]rest of the cell? 0:05:51.760,0:05:53.140 This is the inside[br]of the cell. 0:06:00.370,0:06:06.360 And so this area is what the[br]actin filaments and the myosin 0:06:06.360,0:06:09.350 heads and all of the rest,[br]and the troponin, and the 0:06:09.350,0:06:12.230 tropomyosin-- they're all[br]exposed to the environment 0:06:12.230,0:06:13.320 that is over here. 0:06:13.320,0:06:15.280 So you can imagine-- I could[br]just draw it here 0:06:15.280,0:06:16.530 just to make it clear. 0:06:21.480,0:06:22.690 I'm drawing it very abstract. 0:06:22.690,0:06:24.480 We'll see more of the structure[br]in a future video. 0:06:38.650,0:06:40.870 This is a very abstract drawing,[br]but I think this'll 0:06:40.870,0:06:42.650 give you a sense of[br]what's going on. 0:06:42.650,0:06:45.510 So let's say this neuron-- and[br]we'll call this a motor 0:06:45.510,0:06:54.380 neuron-- it's signaling for[br]a muscle contraction. 0:06:54.380,0:06:57.610 So first of all, we know how[br]signals travel across neurons, 0:06:57.610,0:07:01.100 especially across axons with[br]an action potential. 0:07:01.100,0:07:04.460 We could have a sodium[br]channel right here. 0:07:04.460,0:07:07.410 It's voltage gated so you have[br]a little bit of a positive 0:07:07.410,0:07:08.500 voltage there. 0:07:08.500,0:07:12.420 That tells this voltage gated[br]sodium channel to open up. 0:07:12.420,0:07:16.160 So it opens up and allows even[br]more of the sodium to flow in. 0:07:16.160,0:07:18.340 That makes it a little bit[br]more positive here. 0:07:18.340,0:07:21.880 So then that triggers the next[br]voltage gated channel to open 0:07:21.880,0:07:25.010 up-- and so it keeps traveling[br]down the membrane of the 0:07:25.010,0:07:28.410 axon-- and eventually, when you[br]get enough of a positive 0:07:28.410,0:07:32.590 threshold, voltage gated calcium[br]channels open up. 0:07:36.060,0:07:37.680 This is all a review[br]of what we learned 0:07:37.680,0:07:39.740 in the neuron videos. 0:07:39.740,0:07:41.760 So eventually, when it gets[br]positive enough close to these 0:07:41.760,0:07:44.290 calcium ion channels, they[br]allow the calcium 0:07:44.290,0:07:46.300 ions to flow in. 0:07:46.300,0:07:50.060 And the calcium ions flow in and[br]they bond to those special 0:07:50.060,0:07:53.950 proteins near the synaptic[br]membrane or the presynaptic 0:07:53.950,0:07:54.850 membrane right there. 0:07:54.850,0:07:56.010 These are calcium ions. 0:07:56.010,0:08:00.990 They bond to proteins that[br]were docking vesicles. 0:08:00.990,0:08:08.170 Remember, vesicles were just[br]these membranes around 0:08:08.170,0:08:09.420 neurotransmitters. 0:08:13.250,0:08:17.500 When the calcium binds to those[br]proteins, it allows 0:08:17.500,0:08:18.840 exocytosis to occur. 0:08:18.840,0:08:22.850 It allows the membrane of the[br]vesicles to merge with the 0:08:22.850,0:08:25.190 membrane of the actual[br]neuron and the 0:08:25.190,0:08:26.600 contents get dumped out. 0:08:26.600,0:08:28.670 This is all review from[br]the neuron videos. 0:08:28.670,0:08:31.470 I explained it in much more[br]detail in those videos, but 0:08:31.470,0:08:32.490 you have-- all of these 0:08:32.490,0:08:34.500 neurotransmitters get dumped out. 0:08:34.500,0:08:38.809 And we were talking about the[br]synapse between a neuron and a 0:08:38.809,0:08:39.450 muscle cell. 0:08:39.450,0:08:41.059 The neurotransmitter[br]here is acetylcholine. 0:08:47.130,0:08:49.320 But just like what would happen[br]at a dendrite, the 0:08:49.320,0:08:53.990 acetylcholine binds to receptors[br]on the sarcolemma or 0:08:53.990,0:08:57.410 the membrane of the muscle cell[br]and that opens sodium 0:08:57.410,0:08:58.820 channels on the muscle cell. 0:08:58.820,0:09:02.330 So the muscle cell also has a a[br]voltage gradient across its 0:09:02.330,0:09:07.210 membrane, just like[br]a neuron does. 0:09:07.210,0:09:11.150 So when this guy gets some[br]acetylcholene, it allows 0:09:11.150,0:09:16.240 sodium to flow inside[br]the muscle cell. 0:09:16.240,0:09:18.580 So you have a plus there and[br]that causes an action 0:09:18.580,0:09:19.990 potential in the muscle cell. 0:09:19.990,0:09:22.510 So then you have a little bit[br]of a positive charge. 0:09:22.510,0:09:26.680 If it gets high enough to a[br]threshold level, it'll trigger 0:09:26.680,0:09:29.100 this voltage gated channel right[br]here, which will allow 0:09:29.100,0:09:32.380 more sodium to flow in. 0:09:32.380,0:09:35.080 So it'll become a little[br]bit positive over here. 0:09:35.080,0:09:37.035 Of course, it also has potassium[br]to reverse it. 0:09:37.035,0:09:38.870 It's just like what's going[br]on in a neuron. 0:09:38.870,0:09:41.970 So eventually this action[br]potential-- you have a sodium 0:09:41.970,0:09:43.170 channel over here. 0:09:43.170,0:09:44.780 It gets a little bit positive. 0:09:44.780,0:09:47.710 When it gets enough positive,[br]then it opens up and allows 0:09:47.710,0:09:49.750 even more sodium to flow in. 0:09:49.750,0:09:51.250 So you have this action[br]potential. 0:09:51.250,0:09:53.230 and then that action potential--[br]so you have a 0:09:53.230,0:09:57.950 sodium channel over here-- it[br]goes down this T-tubule. 0:09:57.950,0:10:00.230 So the information from the[br]neuron-- you could imagine the 0:10:00.230,0:10:03.930 action potential then turns into[br]kind of a chemical signal 0:10:03.930,0:10:06.370 which triggers another[br]action potential that 0:10:06.370,0:10:07.880 goes down the T-tubule. 0:10:07.880,0:10:10.560 And this is the interesting[br]part-- and actually this is an 0:10:10.560,0:10:13.670 area of open research right[br]now and I'll give you some 0:10:13.670,0:10:17.860 leads if you want to read more[br]about this research-- is that 0:10:17.860,0:10:20.940 you have a protein complex that[br]essentially bridges the 0:10:20.940,0:10:23.010 sarcoplasmic reticulum[br]to the T-tubule. 0:10:23.010,0:10:28.600 And I'll just draw it as[br]a big box right here. 0:10:28.600,0:10:31.180 So you have this protein[br]complex right there. 0:10:31.180,0:10:34.970 And I'll actually show it--[br]people believe-- I'll sort 0:10:34.970,0:10:36.270 some words out here. 0:10:36.270,0:10:44.170 It involves the proteins[br]triadin, junctin, 0:10:44.170,0:10:51.180 calsequestrin, and ryanodine. 0:10:56.290,0:10:59.550 But they're somehow involved in[br]a protein complex here that 0:10:59.550,0:11:04.550 bridges between the T-tubule the[br]sarcoplasmic verticulum, 0:11:04.550,0:11:06.720 but the big picture is what[br]happens when this action 0:11:06.720,0:11:09.880 potential travels down here--[br]so we get positive enough 0:11:09.880,0:11:16.280 right around here, this complex[br]of proteins triggers 0:11:16.280,0:11:17.610 the release of calcium. 0:11:17.610,0:11:20.920 And they think that the[br]ryanodine is actually the part 0:11:20.920,0:11:23.930 that actually releases the[br]calcium, but we could just say 0:11:23.930,0:11:27.790 that it-- maybe it's triggered[br]right here. 0:11:27.790,0:11:30.330 When the action potential[br]travels down-- let me switch 0:11:30.330,0:11:31.010 to another color. 0:11:31.010,0:11:33.100 I'm using this purple[br]too much. 0:11:33.100,0:11:36.980 When the action potential gets[br]far enough-- I'll use red 0:11:36.980,0:11:40.070 right here-- when the action[br]potential gets far enough-- so 0:11:40.070,0:11:42.260 this environment gets a little[br]positive with all those sodium 0:11:42.260,0:11:45.920 ions flowing in, this mystery[br]box-- and you could do web 0:11:45.920,0:11:47.100 searches for these proteins. 0:11:47.100,0:11:49.030 People are still trying to[br]understand exactly how this 0:11:49.030,0:11:52.570 mystery box works-- it triggers[br]an opening for all of 0:11:52.570,0:11:57.290 these calcium ions to escape[br]the sarcoplasmic reticulum. 0:11:57.290,0:12:03.870 So then all these calcium ions[br]get dumped into the outside of 0:12:03.870,0:12:07.610 the sarcoplasmic reticulum[br]into-- just the inside of the 0:12:07.610,0:12:10.230 cell, into the cytoplasm[br]of the cell. 0:12:10.230,0:12:12.550 Now when that happens, what's[br]doing to happen? 0:12:12.550,0:12:14.670 Well, the high calcium[br]concentration, the calcium 0:12:14.670,0:12:17.390 ions bond to the troponin, just[br]like what we said at the 0:12:17.390,0:12:18.750 beginning of the video. 0:12:18.750,0:12:23.390 The calcium ions bond to the[br]troponin, move the tropomyosin 0:12:23.390,0:12:26.520 out of the way, and then the[br]myosin using ATP like we 0:12:26.520,0:12:30.050 learned two videos ago can start[br]crawling up the actin-- 0:12:30.050,0:12:35.030 and at the same time, once the[br]signal disappears, this thing 0:12:35.030,0:12:39.290 shuts down and then these[br]calcium ion pumps will reduce 0:12:39.290,0:12:41.180 the calcium ion concentration[br]again. 0:12:41.180,0:12:45.070 And then our contraction will[br]stop and the muscle will get 0:12:45.070,0:12:46.090 relaxed again. 0:12:46.090,0:12:49.070 So the whole big thing here is[br]that we have this container of 0:12:49.070,0:12:52.440 calcium ions that, when the[br]muscles relax, is essentially 0:12:52.440,0:12:55.330 taking the calcium ions out of[br]the inside of the cell so the 0:12:55.330,0:12:58.830 muscle is relaxed so that you[br]can't have your myosin climb 0:12:58.830,0:13:00.330 up the actin. 0:13:00.330,0:13:03.190 But then when it gets the[br]signal, it dumps it back in 0:13:03.190,0:13:06.040 and then we actually have a[br]muscle contraction because the 0:13:06.040,0:13:11.280 tropomyosin gets moved out of[br]the way by the troponin., So I 0:13:11.280,0:13:12.090 don't know.[br]That's pretty fascinating. 0:13:12.090,0:13:14.160 It's actually even fascinating[br]that this is still not 0:13:14.160,0:13:16.200 completely well understood. 0:13:16.200,0:13:19.140 This is an active-- if you want[br]to become a biological 0:13:19.140,0:13:21.360 researcher, this could be an[br]interesting thing to try to 0:13:21.360,0:13:22.330 understand. 0:13:22.330,0:13:25.740 One, it's interesting just from[br]a scientific point of 0:13:25.740,0:13:27.900 view of how this actually[br]functions, but there's 0:13:27.900,0:13:31.630 actually-- there's maybe[br]potential diseases that are 0:13:31.630,0:13:34.210 byproducts of malfunctioning[br]proteins right here. 0:13:34.210,0:13:37.050 Maybe you can somehow make these[br]things perform better or 0:13:37.050,0:13:37.770 worse, or who knows. 0:13:37.770,0:13:41.960 So there actually are positive[br]impacts that you could have if 0:13:41.960,0:13:44.750 you actually figured out what[br]exactly is going on here when 0:13:44.750,0:13:47.440 the action potential[br]shows up to open up 0:13:47.440,0:13:48.490 this calcium channel. 0:13:48.490,0:13:49.770 So now we have the[br]big picture. 0:13:49.770,0:13:53.770 We know how a motor neuron can[br]stimulate a contraction of a 0:13:53.770,0:14:00.240 cell by allowing the[br]sarcoplasmic reticulum to 0:14:00.240,0:14:03.490 allow calcium ions to travel[br]across this membrane in the 0:14:03.490,0:14:04.590 cytoplasm of the cell. 0:14:04.590,0:14:07.240 And I was doing a little bit of[br]reading before this video. 0:14:07.240,0:14:08.740 These pumps are very[br]efficient. 0:14:08.740,0:14:11.980 So once the signal goes away and[br]this door is closed right 0:14:11.980,0:14:16.900 here, this this sarcoplasmic[br]reticulum can get back the ion 0:14:16.900,0:14:19.070 concentration in about[br]30 milliseconds. 0:14:19.070,0:14:22.100 So that's why we're so good at[br]stopping contractions, why I 0:14:22.100,0:14:25.820 can punch and then pull back my[br]arm and then have it relax 0:14:25.820,0:14:28.870 all within split-seconds[br]because we can stop the 0:14:28.870,0:14:33.520 contraction in 30 milliseconds,[br]which is less 0:14:33.520,0:14:34.670 than 1/30 of a second. 0:14:34.670,0:14:37.500 So anyway, I'll see in the next[br]video, where we'll study 0:14:37.500,0:14:40.030 the actual anatomy of[br]a muscle cell in a 0:14:40.030,0:14:41.840 little bit more detail.