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The Journal of Neuroscience, April 15, 1998, 18(8):2849-2855
N- and P/Q-Type Ca2+ Channels Mediate Transmitter
Release with a Similar Cooperativity at Rat Hippocampal Autapses
Christopher A.
Reid,
John M.
Bekkers, and
John D.
Clements
Division of Neuroscience, John Curtin School of Medical Research,
Australian National University, Canberra ACT 0200, Australia
The relationship between extracellular Ca2+
concentration and EPSC amplitude was investigated at excitatory
autapses on cultured hippocampal neurons. This relationship was steeply
nonlinear, implicating the cooperative involvement of several
Ca2+ ions in the release of each vesicle of
transmitter. The cooperativity was estimated to be 3.1 using a power
function fit and 3.3 using a Hill equation fit. However, simulations
suggest that these values underestimate the true cooperativity. The
role of different Ca2+ channel subtypes in shaping
the Ca2+ dose-response relationship was studied
using the selective Ca2+ channel blockers
 -agatoxin GIVA (-Aga), which blocks P/Q-type channels, and
-conotoxin GVIA (-CTx), which blocks N-type channels. Both
blockers broadened the dose-response relationship, and the Hill
coefficient was reduced to 2.5 by -Aga and to 2.6 by -CTx. This
broadening is consistent with a nonuniform distribution of Ca2+ channel subtypes across presynaptic terminals.
The similar Hill coefficients in -Aga or -CTx suggest that there
was no difference in the degree of cooperativity for transmitter
release mediated via N- or P/Q-type Ca2+ channels. A
model of the role of calcium in transmitter release is developed. It is
based on a modified Dodge-Rahamimoff equation that includes a
nonlinear relationship between extracellular and intracellular
Ca2+ concentration, has a cooperativity of 4, and
incorporates a nonuniform distribution of Ca2+
channel subtypes across presynaptic terminals. The model predictions are consistent with all of the results reported in this study.
Key words:
calcium channel; synaptic transmission; cooperativity; -agatoxin GIVA; -conotoxin GVIA; synaptic terminal; vesicle
release complex
Copyright © 1998 Society for Neuroscience 0270-6474/98/1882849-07$05.00/0
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