Biophysical and Pharmacological Characterization of Voltage-dependent Ca2+
Channels in Neurons Isolated from Rat Nucleus Accumbens.
Dennis Churchill and Brian A. MacVicar.
Neuroscience Research Group, Department of Medical Physiology, Faculty of
Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Phone: (403)220-
4594, Fax: (403)283-2700, email: macvicar@acs.ucalgary.ca.
APStracts 4:271N, 1997.
ABSTRACT
The nucleus accumbens (NA) has an integrative role in behavior and may mediate
addictive and psychotherapeutic drug action. Whole-cell recording techniques
were used to characterize electrophysiologically and pharmacologically high-
and low-threshold voltage-dependent Ca2+ currents in isolated NA neurons.
High-threshold Ca2+ currents, which were found in all neurons studied and
include both sustained and inactivating components, activated at potentials
greater than -50 mV and reached maximal activation at around 0 mV. In contrast
low-threshold Ca2+ currents activated at voltages greater than -64 mV with
maximal activation occurring at -30 mV. These were observed in 42% of acutely-
isolated neurons. Further pharmacological characterization of high-threshold
Ca2+ currents was attempted using nimodipine (Nim), (-conotoxin-GVIA ((-CgTx)
and (-agatoxin-IVA ((Aga) which are thought to identify the L-, N- and P/Q
subtypes of Ca2+ currents, respectively. Nim (5-10 (M) blocked 18%, (CgTx (1-2
(M) blocked 25% and (Aga (200 nM) blocked 17% of total Ca2+ current. Nim
primarily blocked a sustained high-threshold Ca2+ current in a partially-
reversible manner. In contrast (CgTx irreversibly blocked both sustained and
inactivating components. (Aga irreversibly blocked only a sustained component.
In all three of these Ca2+ channel blockers, plus 5 (M (-conotoxin-MVIIC to
eliminate a small unblocked Q-type Ca2+ current (7%), a toxin-resistant high-
threshold Ca2+ current remained that was 32% of total Ca2+ current. This
current inactivated much more rapidly than the other high-threshold Ca2+
currents, was depressed in 50 (M Ni2+ and reached maximal activation 5-10 mV
negative to the toxin-sensitive high-threshold Ca2+ currents. Thus, NA neurons
have multiple types of high-threshold Ca2+ currents with a large component
being the toxin-resistant "R" component.
Received 31 January 1997; accepted in final form 22 September 1997.
APS Manuscript Number J97-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997