 Fatigue of a muscle happens when that muscle can't sustain its expected power output. So for whatever reason, the muscle is attempting to contract, but the contraction is not as strong as you would hope or you would expect it to be. There are two categories of fatigue, and it's important to distinguish between them. There is central fatigue and peripheral fatigue, peripheral, peripheral. Central fatigue is basically the feeling of being tired. Central fatigue comes from the central nervous system, so it's a message from the central nervous system, and it isn't an objective thing we can quantify. It's actually a subjective feeling. It's the, oh, really? I really have to run one more mile? Please no, I'm tired. That's central fatigue. Central fatigue usually comes first, and the hypothesis is that central fatigue precedes peripheral fatigue because it's protective. Before you can really basically do some physiological damage, your brain says, you know what? I'm feeling kind of weary over here. Why don't we call it good before we start doing some damage? Peripheral fatigue is basically any decrease in power output that happens from the synapse or the neuromuscular junction on. So anywhere from here, this is my little skeletal muscle, from here on, this would be a possible cause of peripheral fatigue, so let me give you some examples. For example, decreased acetylcholine. Why would that cause fatigue? For whatever reason, you're firing, firing, firing, firing your somatic motor neuron, and the somatic motor neuron doesn't have time to replenish its acetylcholine reserves. You could actually run out of acetylcholine and therefore not be able to fire your muscle as effectively. This is probably not a factor in most situations. It might be a factor in super, super intense workouts, but in most situations it isn't. Probably the characteristic that does play a role most often is decreased energy supplies. That says energy, of course it does. And it's not just energy in the form of ATP, it's energy, it's basically the supplies needed to make ATP. And thinking back on your Bio 1 Glory days, you remember that we need glucose and we need oxygen in order to produce ATP. The glucose in muscles and skeletal muscles and in your body, glucose is stored in the form of glycogen. And glycogen is basically an animal version of starch in plants. And starch is just a whole bunch of glucose molecules stuck together. And glycogen is our version of this. Glycogen is how we store our glucose so that we can use it when we need it. Glycogen is stored in your liver and it's also stored in your skeletal muscles. It's the primary source of glucose during exercise or working out. If you don't have enough glycogen to produce sugar or produce your ATP, then that can lead to fatigue. This is actually the best hypothesis for what really is happening when muscles go through physiological fatigue. Oxygen is also an issue, though. And we know that we're going to talk about different kinds of muscle cells in the next piece and they use oxygen differently. And that oxygen is, if you don't have that, you're super limited in how much work your muscles can do. Sometimes you end up with garbage as a byproduct. And one of the things that they think might be a player is when we break down our ATP into ADP plus P, they think that the P, of course, they think that the P actually binds with calcium and then removes, like, makes the calcium unable to do, to play its role in the muscle contraction itself. So if you end up with breaking down a whole bunch of ATP in your skeletal muscle, you'll end up with a whole bunch of extra phosphates that are just floating around. Those phosphates combine with the calcium and make that calcium unable to do its job of helping facilitate the muscle contraction itself. There's also an argument that maybe potassium is playing a role. And we know that in the nicotinic acetylcholine receptors, they serve as sodium channels, but potassium can also get through those things. And if the muscle fiber is stimulated over and over again, then sodium is going to get in, but also a little bit of potassium over time is going to get out. And you can imagine that that is going to change the membrane potential of the skeletal muscle cell. And if you change the membrane potential, you get more difficult to fire. Did you follow that? Of course. So potassium in the extracellular fluid, that's an argument that might be a case. They also think, and this one probably makes sense to you and you would have thought of this on your own, they also think that an increase in lactic acid might change the pH. Lactic acid is kind of a controversial subject and our understanding of lactic acid is changing a lot right now. And so they're not quite sure about this one, but it's something that we often think about. These things are physiological. This is more psychological. Although it's physiological in the sense that they do think there is a protective function in this like, dude, really, why do you want me to climb that hill yet again? That seems really crazy. In lecture, we will watch a video of Shawn Welch and Wendy Ingram in the 1997 Hawaii Iron Man. And we will try to figure out are those ladies experiencing central muscle fatigue or peripheral muscle fatigue? And if you really can't stand it, you should go check it out because it makes me cry every single time I watch it because it's like unbelievably inspiring and insane. Okay, so the next thing we're going to talk about are the different kinds of myofibers and it relates to this because these characteristics, these qualities are different in different kinds of muscle cells.