An illustrated introduction to GABA-A receptor action.
This is the mechanism of action of alprazolam on the gaba a receptor of gabaergic neurons and the larger effects so let’s dive in first this is a list of the steps that we’re going to go through so binding of alprazolam increases the affinity of the gaba a receptor for binding gaba next negatively charged chloride ions flow into the dendrite of this neuron
Hyperpolarization happens which constitutes an inhibitory presynaptic potential we’ll get to that over here likelihood of an action potential is decreased and finally an anxiolytic or anti-anxiety effect so in more detail here we go this is an illustration of the alprazolam when it binds to this allosteric site it acts as an agonist by increasing the affinity
Of the gaba a receptor for binding gaba oh my god my cat is about to walk into the frame shattering right now um when this happens and gaba can bind note that they have different binding sites on different subunits of the receptor but when they’re bound it allows for a conformational change and chloride ions to flow into the dendrites so we get an influx of
Negative ions um here we have inside the intracellular space of the neuron there is what’s called a potential and normally that resting potential is about negative 70 millivolts and that’s maintained by this sodium potassium pump which is active transport uses atp and then there’s the um potassium leak channels so that’s normally responsible for maintaining
Our negative 70 millivolts but when we get an influx of negative charged ions we get what’s called hyperpolarization so the neuron becomes even more negatively charged than it would normally be so this hyperpolarization this negative charge flows down the dendrite to the soma of the neuron and it gets summated with lots of other different signals coming in
On the dendrites that are on other parts of the neuron so they all get summated and this is the axonal hillock right here and so what happens is we get let’s say excitatory we’re getting closer to that threshold of when an action potential is going to happen or if we get an inhibitory like this hyperpolarization it’s going to go more polarized in the negative
Direction and further away from this action potential threshold so when we have this negative influx this acts to keep the charge of our neuron below the action potential threshold so we do not get an action potential or it’s significantly less likely so this is zooming in on this here we have a figure it shows us the millivolts of the different states of the
Neuron so our normal action potential is this bright yellow it would go all the way up to depolarized completely in the positive direction and then goes back down to a little below resting and then gets reestablished with our gaba inhibition it’s not going to go that far above resting and it’s probably going to stay beneath it so we never get an action potential
So where are we now the likelihood of an action potential has decreased so if that action potential does not happen does not travel down the axon does not reach synapse we are going to get a resultant inhibition via lack of excitation to these brain areas for example so we have the basal ganglia and the resultant inhibition is a muscle relaxing effect then the
Locus cyrillius calms cognitive arousal and the limbic system inhibition results in decreased fear and anxiety so that’s our all over anti-anxiety effect from cellular to on a larger brain scale
Transcribed from video
Alprazolam (Xanax) Effect: Cellular Mechanism and Larger Impact By Elizabeth Bates
