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Volume 17, Number 12,
Issue of June 15, 1997
pp. 4570-4579
Copyright ©1997 Society for Neuroscience
Comparison of N- and P/Q-Type Voltage-Gated Calcium Channel
Current Inhibition
Received Dec. 2, 1996; revised March 26, 1997; accepted March 31, 1997.
Kevin P. M. Currie and
Aaron P. Fox
The Department of Pharmacological and Physiological Sciences, The
University of Chicago, Chicago, Illinois 60637
Activation of N- and P/Q-type voltage-gated calcium channels
triggers neurotransmitter release at central and peripheral synapses. These channels are targets for regulatory mechanisms, including inhibition by G-protein-linked receptors. Inhibition of P/Q-type channels has been less well studied than the extensively characterized inhibition of N-type channels, but it is thought that they are inhibited by similar mechanisms although possibly to a lesser extent
than N-type channels. The aim of this study was to compare the
inhibition of the two channel types.
Calcium currents were recorded from adrenal chromaffin cells and
isolated by the selective blockers  -conotoxin GVIA (1 µM) and -agatoxin IVA (400 nM). The
inhibition was elicited by ATP (100 µM) or intracellular
application of GTP- -S. It was classified as voltage-sensitive
(relieved by a conditioning prepulse) or voltage-insensitive (present
after a conditioning prepulse). The voltage-insensitive inhibition
accounted for a 20% reduction of both currents, whereas the
voltage-sensitive inhibition reduced the N-type current by 45% but the
P/Q-type current by 18%. However, the voltage dependence of the
inhibition, the time course of relief from inhibition during a
conditioning prepulse, and the time course of reinhibition after such a
prepulse showed few differences between the N- and P/Q-type channels.
Assuming a simple bimolecular reaction, our data suggest that changes
in the kinetics of the G-protein/channel interaction alone cannot
explain the differences in the inhibition of the N- and P/Q-type
calcium channels. The subtle differences in inhibition may facilitate
the selective regulation of neurotransmitter release.
Key words:
calcium channel;
G-protein;
ATP;
inhibition;
patch clamp;
GTP--S;
N-type calcium channel;
P/Q-type calcium channel
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