5.0 Calcium and Transmitter release in a nerve terminal
The role of calcium in the release of transmitter from a nerve
terminal is a
fascinating problem. Since the
most elegant demonstration by Katz and Melidi that for release to
occur, calcium
must be present in the medium at the synaptic region at the time
of arrival
of the impulse, the problem has drawn the attention of many
investigations.
The essence of what is known about the role of Ca++ in
transmitter release
can be summarized as follows.
- The entry of calcium into terminals has been shown so
consistently and
clearly by numerous experiments, direct and indirect, that it has
become dogma.
- A relatively small part of the Ca which enters is free to
diffuse because it
binds to a variety of strong intracellular chelators.
The result of this binding in turn causes:
- a reduction in
the rate of
diffusion of Ca away from the membrane, making Ca extrusion more
efficient
- facilitation of release in impulses following closely in
time can only be explained via simulations which include this
binding
- reactions which produce 2nd messengers
- putative reactions involved in the docking of vesicles on
the membrane and
release of transmitter
- There is evidence of a Na/Ca exchange mechanism in the
terminal which
would enhance both:
- the entry of Ca during the
depolarizing phase of
the impulse and
- the extrusion of Ca afterwards.
- This strong evidence of a metabolically driven pump which
extrudes Ca.
A multitude of investigators are now using a wide variety of
techniques, ranging from Ca-dye imaging to molecular biology, in
an effort to work out the dtetails of these facets. This effort
is perhaps most intense in trying to determine the many steps in
the docking, extrusion, re-uptake, refilling, and priming the
synaptic vesicles.
I have included here a reproduction of some of our
simulations involving this machinery.