[MUSIC] Okay, so we have an action potential coming down the line, down the axon, and we have. Neurotransmitters that are packaged within vesicles. How we get those, the neurotransmitter out of the vesicle and across, out of the cell and able to go and effect another cell. Well to understand this we have to realize that. There is a, there's a cell membrane, but the cell also has a lot of other membranes that are inside. Inside in these things called organelles. So, for instance, there's a nuclear envelope and nuclear membrane. There are mitochondria. These are the power houses of the cell. There is endoplasmic particulum where all the proteins are made so the manufacturing cell center of the cell. There are endosomes and lysosomes, which are basically the garbage collectors of the cell, and all of these are surrounded by. Membranes. And so, in order and there are vesicles that traffic the proteins from the endoplasmic reticulum out to the appropriate place. So, some proteins are going to go to the membranes. Some are going to go to these other places. So the fusion between two different membranes, between say the endoplasmic reticulum membrane and the membrane of a vesicle that's going to traffic a protein to some place. That happens all the time. It happens constitutively. And so our challenge, as a neuron, is to stop that. We can't have these vesicles fusing with the plasma membrane, with the cell membrane all the time. That would be, that would not. Work, what we want to do is we want to make the vesicle fuse to the membrane only when the action potential arrives. So the key to neurotransmitter release is two things. Number one, we're going to suppress constitutive release. Suppress constitutive or ongoing release and number two, we are going to link the release that we want. We are going to link release in the synaptic terminal to the action potential. So we are going to link release. To the action potential. And the way that we do that, first of all there is a molecule that suppresses constitutive release within the synaptic terminal. So that's great, so that's done. Now let's think about how do we link release to the action potential. Well, when the action potential comes down, this the membrane potential, remember that the membrane potential, if this is zero ground, the membrane potential's around negative 65 millivolts. But. In comes that action potential, and it goes skyrocketing, and as this potential increases, it opens a particular type of ion channel that lets in a for, we haven't talked about this ion, but it's a very important ion. It let's in calcium ions. These are positively charged, they lost, oops, forgot two electrons, so they've got a, a two positive charges. And, these calcium ions are going to flood in to the synaptic terminal, and that is going to trigger release. The release that happens. Of vesicles that contain neurotransmitters is only happens when the calcium concentration increases. And the calcium concentration only increases when the action potential arrives. So now we have accomplished our goal. We suppressed the constitutive release and now we've, we've linked the release to the action potential. And all that happens when the calcium concentration increases is that this vesicular membrane and the the cell membrane. They actually,. They're not just close, they fuse and so you get something that looks like this. Calcium comes in and now these two touch and then it looks something like this. It opens, this joins and it opens and then that goes to a bigger opening and then they're just, it's all one. So now we've released neurotransmitter but the key point was that we didn't particularly release, it's not like we pumped it out, we simply fused the vesicle membrane. To the cell membrane. In the next segment we're going to look at a very important drug that affects this process. [MUSIC]