Synaptic communication and re-uptake / reuptake inhibitors / Adrafinil

r norman rsn_ at _comcast.net
Wed Dec 15 08:47:19 EST 2004


On Wed, 15 Dec 2004 13:38:11 +0100, 1234 <123412 at 101.com> wrote:

>Hi all,
>I have read some stuff about neurology over the internet. There is one 
>thing I don't understand about the synaptic communication:
>
>A neuron releases a neurotransmitter in the synapse to communicate with 
>another neuron.  Now the second neuron is stimulated and active until 
>the re-uptake clears up the neurotransmitter from there, is this correct?
>
>How much time does it take for the re-uptake mechanism to clear up 
>everything? I suppose it should be something in the order of magnitude 
>of seconds, otherwise an old idea/reasoning wouldn't go out of our mind 
>and we wouldn't be able to think to something else, correct?
>
>In this scenario, what is the purpose of the re-uptake inhibitors? To 
>confuse our minds by making the old reasonings last in our mind for 
>hours instead of seconds?
>
>
>Also how could things like Adrafinil (norepinephrine agonist) work? Is 
>it stored in vesicules at the end of axons together with the 
>norepinephrine and released into the synapses together with it?
>
>Is it subject to the same re-uptake as the norepinephrine or it stays in 
>the synaptic cleft for a long time until slowly goes to the plasma? (if 
>latter: it would cause roughly the same effect of a reuptake inhibitor, 
>right?)
>

After a pre-synaptic neuron releases its transmitter and it acts on
the post-synaptic receptors, there are three different mechanisms to
eliminate the transmitter.  First, there may be enzymes in the
extracellular space (attached to the membranes of either neuron) that
break down the transmitter.   Second, there may be transport proteins
in the presynaptic membrane that take the transmitter back into the
presynaptic cell.  This is the reuptake mechanism you describe.
Similarly, there may be transport proteins that take the transmitter
into nearby glial cells.  Third, the transmitter might simply diffuse
away making its concentration so low that it is no longer effective.
These can also work in combination.

All these act in a time frame measured in milliseconds.  After some
tens of milliseconds, the transmitter is completely removed from the
synaptic region.  The duration of synaptic action is normally much
shorter than the duration of the post-synaptic effect.  That is, the
post-synaptic potential far outlasts the presence of synaptic
transmitter.  

In synapses where reuptake is the primary removal mechanism, reuptake
inhibitors allow the transmitter to persist in the synaptic space for
a much longer time than normal and hence to produce a much increased
response.  "Much longer" means  only many more milliseconds.  The
times are nowhere near the seconds and hours you mention. 

You mention "ideas" and "reasonings" in our "mind". Certainly these
are important notions in thinking about human brain function, but they
are very far removed from synaptic function and nerve cell firing.
Clearly they are related, but the duration of a synaptic potential has
nothing whatsoever to do with the duration of an idea or concept in
the mind.





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