3 - 1 - 22. Drugs Bind to Neurotransmitter Transporters (15-41)

3 - 1 - 22. Drugs Bind to Neurotransmitter Transporters (15-41)

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Hello, we are discussing neurotransmitter transporters. These are very cool molecules, and they are the third major class of targets in drugs and the brain. As usual, we start with a system or a nucleus in the brain that can focus our attention on the target under discussion. And, certainly, for the neurotransmitter transporters. Part of the focus needs to be on the cells that make serotonin, the so called Rathane nuclei. In the midbrain, there are two major systems, the rostral and the caudal. They project to many regions of the brain and modulate synaptic transgression and neuronal excitability in ma-, many areas of the brain. To most experts, the success of selective serotonin re-uptake inhibitors, or SSRI's implies participation of serotonergic systems in depression. In order to understand neurotransmitter transporters, we need to distinguish. Three major classes of proteins that transport ions and other molecules across membranes. We've already discussed ion channels. Ion channels, flux many ions, per confirmational change, that opens or closes them. And we will discuss them further, in this lecture. Two other systems that transport ions include, the active transporters, or pumps, that split ETP, in order to bring, ions across the membrane. There are three major classes of such. Ion pumps. We'll discuss two of them today. But really the hero of the story today, are the ion coupled transporters. These bring small molecules across the membrane, by harnessing the gradient set up by the pumps. Let's explain this a little more. First of all let's talk about how neural transmitters get into pre-synaptic terminals. Of course, sometimes they are made in pre-synaptic terminals. But in addition, after they are released into the synaptic cleft. Sodium coupled with cell membrane neurotransmitter transporters utilize the preexisting sodium concentration gradient that was originally established by the so-called sodium pump. We also call the sodium pump the sodium potassium ATPase. So we have little sodium inside a neuron or inside most cells. We have a lot of sodium outside. And so the cell can utilize this gradient of sodium to drive small organic molecules into the cytosol against their concentration gradient. More on how this occurs in the next mini-lecture. But we have here in the plasma membrane the sodium coupled cell membrane transporter, neurotransmitter transporters, and here we are depicting either the one for serotonin or the
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different one for dopamine. As we'll see, there are several classes of sodium-coupled cell membrane neurotransmitter transporters. Once the neurotransmitter gets into the cytosol there's a second ion-coupled neurotransmitter transporter that brings the transmitter into the synaptic vesicle.
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