3 - 2 - 23. Neurotransmitter Transporters as Molecules (10-59)

3 - 2 - 23. Neurotransmitter Transporters as Molecules (10-59)

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In this final mini lecture on neurotransmitter transporters, we are going to discuss them as proteins, and we're going to count them. It's important to discuss what we call the alternating access model for how ion coupled transporters actually work. They have the problem of linking the transport of an ion to the transport of another small molecule. And so, what the alternating access model says is that the transmitter transporter can exist facing two different compartments. When it faces the outside compartment, it waits for various molecules, various substrates to bind. Then, it undergoes a conformational change which releases those substrates to the other compartment, then it flips back and can do the same thing over and over again as those substrates are available. It can do this either by putting all of the molecules in the same compartment, or by starting with them in different compartments. It's called Symport, meaning transporting together, or Antiport, meaning transport in opposite directions. Now actually, as three dimensional atomic molecules, this is what we know about ion coupled transporters. It's actually not a serotonin transporter, it is a bacterial homologue that actually transports Lucine. But it does bind Fluoxitine in a place where other experiments say, is a reasonable place for fluoxetine to bind to serotonin transporters. So, here's the outside surface of the cell and the inside surface, which I've drawn approximately correctly for the protein molecule. And here is the PDB file which you can retrieve for yourself and examine. Now, this is a, an atomic scale view, but its aesthetic view, and it doesn't give us the alternating access view. So, let's look at some experiments that my group did several years ago, trying to flesh out the alternating access model in a dynamic view. Another way to state the alternating access model, model is that, an ion
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