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Volume 16, Number 12,
Issue of June 15, 1996
pp. 3848-3861
Copyright ©1996 Society for Neuroscience
Muscarinic Activation of a Voltage-Dependent Cation Nonselective
Current in Rat Association Cortex
Received Oct. 19, 1995; revised March 18, 1996; accepted March 21, 1996.
Samir Haj-Dahmane and
Rodrigo Andrade
Department of Psychiatry and Behavioral Neuroscience, Wayne State
University School of Medicine, Detroit, Michigan 48201
The ionic mechanism underlying the acetylcholine-induced
depolarization of layer V pyramidal neurons of rat prefrontal cortex
was examined using whole-cell recording in in vitro rat
brain slices. Consistent with previous results, pressure application of
acetylcholine to layer V pyramidal neurons elicited a strong
depolarization. Pharmacological analysis of this response indicated
that it was mediated by the stimulation of muscarinic receptors as it
was mimicked by muscarinic agonists, but not by nicotine, and was
blocked by atropine.
The inward current responsible for the depolarization resulted from the
activation of a voltage-dependent, cation nonselective current. Thus,
the amplitude of the current was critically dependent on extracellular
sodium concentration but not on extracellular potassium or chloride
concentration. Examination of the I-V
relationship for the muscarinic current using voltage clamp revealed
that the current reversed near 15 mV and exhibited a strong voltage
dependence, turning off rapidly in the subthreshold range. The voltage
dependence of the current led to the appearance of a current associated
with a conductance decrease when examined using steady-state voltage-
or current-clamp measurements. This might have led to earlier
misidentification of this response as mediated by a decrease in
potassium conductance.
These results question the traditional interpretation that muscarinic
depolarization in cortex is mediated by a decrease in potassium
conductance. They indicate that the fundamental mechanism responsible
for muscarinic depolarization in prefrontal cortex involves the
activation of a voltage-dependent, cation nonselective current. This
current might represent a previously unsuspected mechanism capable of
mediating slow depolarization in the central nervous system.
Key words:
acetylcholine;
muscarinic receptors;
depolarization;
cation nonselective current;
pyramidal neurons;
cerebral cortex
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