[MUSIC] Okay, so let's talk about Botox. Botox is one of several clostridial toxins made by clostridial bacteria. And the full name of Botox is actually botulinum toxin. And to understand what botulinum toxin does, we need to know one more thing. What I told you is that the vesicles are held very close to the cell membrane. What holds them? A group of three proteins, two of them anchored in the cell membrane, one of them anchored in the vesicle membrane, the details don't matter so much. But this complex is called the snare complex. And what happens is that when calcium comes in, it changes its shape. It changes its confirmation and it goes from doing like that to being in a straight line. So that pushes the vesicle into the plasma membrane and fusion Is inevitable, resistance is futile. So you have to, at that point, when they're that close, they have to fuse. It takes a lot of energy for them not to fuse, and when they're that close, it's inevitable. Okay, so it's this snare pin and its the snare pin's sensitivity to calcium that is the final event that allows the vesicle to fuse with the cell membrane. Botox comes in and cuts any one of these, Botox cuts a particular one. But the clostridial toxins cut a variety of places in these three proteins that make up the snare pin. If the snare pin is broken for whatever reason, if that is cut, then release doesn't happen. And it's a simply as that. So what clostridial toxin are doing is blocking release. Now, if you block release. If somebody is administered a sufficient dose of botulinum toxin, the release we that we have to care about is the release from a motor neuron to the diaphragm. The diaphragm is the thing that allows us to breath. Diaphragm is a muscle right here, right in there. And we need our diaphragm to contract. And without the diaphragm we don't breathe, without breathing we don't get oxygen to our brain, and without oxygen in brain we're going to die. So it's a deadly weapon, and when I first started teaching in 1992 or in the 90s, we used to talk about the fact that the clostridial toxins were potential weapons of mass destruction, so to speak. So [COUGH] mass death, anyway. So now we use them all the time. And we use them for very serious problems. Things like focal dystonia where there is an inappropriate continual contraction of a muscle, and that is a basal ganglia disorder. There are a lot of famous people that have focal dystonia. Leon Fleisher is a piano player who has it in his right hand, so these two fingers are always contracted. And Dianne Ream has it in her larynx, so she has laryngeal focal dystonia. And these people are treated with Botox. So the Botox is injected at a very low dose, very locally. So it's blocking the contraction of these fingers in Leon Fleisher's example, and in the Larynx it's blocking the spasmodic contraction of the laryngeal muscles. And it's used for a large variety of treatments of various disorders. It's also used cosmetically. And the interesting about it's use in cosmetics, is that, I don't think that we fully understood, that before the widespread use of Botox, that we make our own wrinkles. There's a lovely quote about how smile lines are really great because they show us how much we been smiling. In fact we are making our wrinkles, and what Botox is doing is preventing the motor neuron from releasing the neurotransmitter on to the muscle, and thereby preventing us from actively making our own wrinkles. Okay, so we've gotten our transmitter release, and now what we're going to talk about is how we've started our expression, we've started our sentence, and now we have to stop our sentence. So we're going to talk about termination of the signal that comes out of a neuron in the next segment. [MUSIC]
