A.3.7. The Chemical Synapse


Purpose:
A chemical synapse transmits electrical signals (= action potentials) from one nerve cell to the next.

Structural and physiological components required:
1. A pre-synaptic membrane in the first nerve cell
2. This pre-synaptic membrane contains Na+, K+ and Ca2+ ion channels.
3. Vesicles in the pre-synaptic cell that contains the (neuro-) transmitter
4. A post-synaptic membrane in the second nerve cell
5. The post-synaptic membrane contains receptor operated channels (=ROC)

A. Function of a chemical synapse:

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1.
A nerve action potential propagates down the axon of the first nerve cell towards the pre-synaptic membrane (thereby opening and closing the relevant Na+ and K+ channels)
2.
When the action potential arrives in the pre-synaptic membrane, it also opens the Ca2+ channels.



Diagram explaining propagation across a chemical synaps
3.
Because of the concentration gradient for calcium, calcium ions will then flow into the cell



4.
This intracellular calcium will induce one of the vesicles to move towards the pre-synaptic membrane


5.
Once at the pre-synaptic membrane, the vesicles will fuse with the membrane and release its content (the neurotransmitter) into the synaptic cleft. This process is called exocytosis (link).
6.
The transmitter diffuses into the synaptic cleft and some of it will reach the post-synaptic membrane
7.
The transmitter can then couple to the receptors located in the post-synaptic membrane
8.
These receptors are linked to ion channels (= receptor operated channels = ROC).
9.
The linkage of the transmitter to the receptor will open that channel.
10.
As more and more transmitters attach to the receptors, more and more channels will open.
11.
Opening the channels will cause a flow of ions in or out of the post-synaptic cell (influx or efflux)
12.
These ions will cause either a depolarization or a hyperpolarization around that membrane
13.
If the membrane depolarizes, then this potential is called an EPSP (= Excitatory Post Synaptic Potential).
14.
If the membrane hyperpolarizes, then this potential is called an IPSP (=Inhibitory Post Synaptic Potential).
Similarities and differences between EPSP and IPSP

B. IPSP’s or EPSP’s?

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1.
Usually, a single pre-synaptic action potential will only cause a small change in potential in the postsynaptic membrane, either a depolarization or a hyperpolarisation.

2.
Whether or not the potential is an EPSP or an IPSP depends on the transmitter, the receptor and the attached ion channel. Some synapses are excitatory (EPSP) while others are inhibitory (IPSP) in nature.
3.
In the case of an IPSP, the membrane potential moves further away from the threshold. This is inhibition as it makes it more difficult for the next action potentials to reach threshold (= inhibition).
4.
In the case of an EPSP, the membrane potential moves closer to the threshold potential but usually does not reach the threshold. Therefore, an action potential is not (yet) generated.
5.
It must be realized that EPSP’s and IPSP’s are local and temporary potential changes. They, for example, do not propagate to the rest of the nerve cell.

6.
Therefore, an EPSP or an IPSP, by itself, has no effect at all. They will only have an effect if something else happens, and that is summation.

7.
Meanwhile, the transmitters in the synaptic cleft and those coupled to the receptors must be removed and inactivated.



8.
They cannot stay there because this would keep the channels open and the membrane in a permanent de- or hyper-polarized state and the whole transmission would be stopped.

9.
Fortunately, there are enzymes in the synapse cleft that break down the neurotransmitters. Often, these broken down components are recycled into the pre-synapse for making new transmitter molecules in new vesicles.

C. Summation of EPSP's and/or IPSP’s

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Examples of summations
1.
In contrast to action potentials, EPSP’s and IPSP’s can summate on ‘top’ of each other (figure).


2.
Because the duration of the EPSP’s is much longer than the action potential, the second EPSP is initiated while the depolarization of the first EPSP is still present.
3.
Therefore, the second EPSP starts at a more depolarized level and achieves a more depolarized value, which is closer to the threshold.

4.
A third EPSP will again start at a higher level and, as shown in the figure, reaches threshold, thereby (finally!) inducing an action potential. That action potential will then propagate to the rest of this nerve cell.
5.
Please notice in this example, that three pre-synaptic potentials were required to generate a single action potential in the post-synaptic membrane.


6.
In general, this ratio is about 10: 1 (10 pres-synaptic potentials are required to make 1 post-synaptic action potential).




D. Important comparisons with the electrical synapse (previous page):

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1.
This process of action potential transmission is much slower than the propagation along a nerve membrane and also much slower than transmission in an electrical synapse.


2.
That is because in an electrical synapse, the speed depends on the flow of ions through the connexons. In a chemical synapse, the speed is mostly determined by the diffusion of the transmitter through the synaptic cleft. This is very much slower.
3.
In contrast to the electrical synapse, the direction of propagation in a chemical synapse is one-directional. If the nerve of the post-synaptic membrane had been first activated, then there are no vesicles in that part of the structure to diffuse back to the pre-synaptic membrane, nor are there ROC’s in the presynaptic membrane for the transmitter to couple to.
4.
In other words, the whole structure of pre- and post-synaptic membranes, of the vesicles and the ROC’s dictates the direction of propagation.



5.
Also, in contrast to the electrical synapse, the ratio of propagation is not 1:1. In general, there are many (approx. ten) action potentials necessary to depolarize the post-synaptic membrane to reach threshold and to generate 1 action potential in the next cell.
6.
This is not the case in an electrical synapse. In an electrical synapse, the ratio is always 1:1.



7.
In the brain, chemical synapses are more common than electrical synapses but in other tissues, especially in the heart and in smooth muscles, electrical synapses are very common.

8.
So the important differences between the electrical and the chemical synapse are:

1. fast vs. slow propagation
2. bi- vs. one-directional
3. 1:1 vs. 10:1 ratio

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A.3.7. The Chemical Synapse

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