primary afferent depolarization

David M. Senseman senseman at lucy.brainlab.utsa.edu
Tue Jan 26 07:36:42 EST 1993

In article <9301251254.AA21883 at xray1.cshl.org> anderson at CSHL.ORG (John Anderson) writes:
>I have been reading 
>  Sykova E. (1991) "Activity-related ionic and volume changes in
>  neuronal microenvironment" in _Volume Transmission in the Brain_ (K.
>  Fuxe, L.F. Agnati, Eds.), pp 317-336, Raven Press, New York.
>In that article, the following statement is made:
>  "[Extracellular] K+ accumulation has been accepted as one of two
>  causal factors (together with GABA) in primary afferent
>  depolarization, which is the mechanism underlying presynaptic
>  inhibition.  It is assumed that the increase in [K+]e that is
>  associated with repetitive neuronal activity reduces transmitter
>  release by curtailing the presynaptic spike amplitude by presynaptic
>  depolarization."
>Could someone please explain this statement?  How does presynaptic
>depolarization reduce the presynaptic spike amplitude?  Seems like it
>should enhance it.

PAD (primary afferent depolarization) isn't all that mysterious.
Why would expect depolarization to ENHANCE transmitter release?
Assuming that the axonal spike completely invades all the terminals,
(probably a reasonable assumption for most systems Eva was 
referring to), then depolarization would DECREASE syanptic release
simply because the membrane potential of the presynaptic terminal
would be closer to V    which is going to be somewhere above +100 mv.

(Hard to do subscripts :)

That means the electrical force driving Ca inward would be reduced 
so that calcium entry during the terminal spike would be reduced.
Since transmitter release is dependent on entry of external Ca,
less transmitter release would occur.

If you get enough PAD so that the terminal membrane is really
depolarized, then additional factors could come into to play
such as channel inactivation.

David M. Senseman, Ph.D.              | Imagine the Creator as a low 
(senseman at lonestar.utsa.edu)          | comedian, and at once the world 
Center for Information Visualization  | becomes explicable.
University of Texas at San Antonio    |               H.L. Mencken 

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