Synaptic transmission and graded potentials

Published on January 31, 2023   36 min
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Hello, and welcome back to fundamentals of human physiology. I'm Charles Sevigny. We're going to continue our discussion today about how neurons function.
So far we've learned about how excitable cells maintain a membrane potential. Meaning that there is the potential there for ions to move across the membrane and actually affect the charge in that membrane. We learned how that works in the context of action potentials through voltage-gated channels and how those are conducted across an axon. Today, we're going to address a few things that we left as a mystery before. So far all we've learned is that an action potential begins at the axon hillock here, travels down the axon. The things we'll focus on today is what happens when it reaches the end of the axon, that's called synaptic transmission. How does it actually take that electrical signal and translate it into something that the next cell can recognize? We need to translate an electrical signal into a chemical signal. We'll talk about that. The other thing we'll discuss is how do we actually start this action potential? How does a neuronal cell body manage various inputs from all these different synapses to decide whether or not it's going to form and initiate an action potential?
Let's start with synaptic transmission. If we zoom in on one of our synapses here and we just need to get some nomenclature under our belts first. The cell in which we have our action potential traveling along, so the first neuron, that's called the presynaptic neuron, the one before the synapse and the cell - it might be a neuron, in this case it is, but it could be by a gland or a muscle or whatever - is called the postsynaptic cell. Because we have neurons here, we'll call it the postsynaptic neuron. We actually have a very elaborate structure here in the synapse. There's a lot of things that aren't shown here. We're going to give a very simplified overview of how synaptic transmission works, because otherwise there's literally an entire course on how this works. Forgive me if I don't go into all the details, but we'll go over the general idea of how this works. What we have is we know we have our action potential traveling down our presynaptic neuron, and that's a depolarizing signal. What happens? The first thing that happens is that that action potential encounters a new type of voltage-gated channel called the voltage-gated calcium channels. Predictably, that causes calcium like we learned before, that calcium has a big drive to want to move inside our cells. It has a very positive equilibrium potential, meaning that even though this cell might be at plus 30 because it's in the middle of an action potential, calcium will still want to move in through those channels. That's what makes calcium such a powerful signaling chemical. Because no matter what really is happening in this cell, no matter how positive it gets, it has such a high equilibrium potential, it will still want to move into the cell. Now, what's happening inside the cell? Inside the cell we have these things called synaptic vesicles. They're basically little power packets made out of similar stuff that the cell membrane is made out of. But inside these synaptic vesicles we have a very high density of neurotransmitter. We'll talk about specific neurotransmitters in a bit. For now we have our neurotransmitter packed in these synaptic vesicles. Very high density, and that tells us something. That in the walls of these synaptic vesicles, we must have some transporter using ATP and active transport to package our neurotransmitter in there in such a high concentration. What happens is when calcium moves into the cell, we have a "series of events." This is where I'm skipping over a lot of detail. But what's going to happen is that these vesicles will 'dock' with the cell membrane here right at the terminal. When they dock, that membrane fuses and they open up, as you can see here, so that our neurotransmitter floods out into this area between our two cells called the synaptic cleft. That's great because now we have a chemical, we've translated our electrical signal into a chemical one. We've sprayed this neurotransmitter out into the synaptic cleft. But it's not going to do anything there unless we have something to recognize it. That's why importantly, on the other side of our membrane, on our postsynaptic cells, we have receptors. Many of these are ligand-gated channels, and by ligand we mean a chemical that comes into contact with them. We had voltage-gated channels before that were shut and open when we have a change in voltage. These are gated channels that are shut and open when they come in contact with their neurotransmitter. We're going to talk about those in a little bit more detail. Depending on what ion those channels allow through will depend on the effect on the postsynaptic neuron. Let's say this channel here allows sodium to move through. Our neurotransmitter comes, it opens the channel, sodium then moves into the cell, and that depolarizes the cell locally on the other side. We'll talk about that a little bit more as we move through. The next thing that we need to deal with is now we have all this neurotransmitter here and we don't want it just continually activating these receptors. We want to be able to fire an action potential, have that neurotransmitter there and then clear it out, so that we can be very specific with the signal that we're trying to transmit. Now, we clear that out in two different ways. One, we'll have reuptake transporters in the presynaptic cell that will suck that transmitter back up into the cell. Depending on the neurotransmitter, these reuptake transporters work in different ways, and sometimes some drugs actually interfere with this so that we actually have a buildup of neurotransmitter in that synapse. We'll talk about that in just a bit. We might have enzymes here that are actually actively metabolizing these neurotransmitters. There are also other cells within our central nervous system called glial cells, that also serve to mop up some of this excess neurotransmitter that might build up there. But either way, we know that we're releasing the neurotransmitter, it's activating our receptors in the postsynaptic cell, then we're clearing it out through a variety of means. That's how a regular synapse works and how synaptic transmission works.