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Vol. 284, Issue 1, 170-179, 1998
Department of Pharmacology and Toxicology, University of Texas
Medical Branch at Galveston, Texas
Corticotropin-releasing factor (CRF) is an important mediator of stress
responses in the brain, and CRF receptors and CRF-containing neurons
and terminals are located within the central nucleus of the amygdala
(CeA). CeA neurons possess multiple types of Ca++ channels,
including L, N and Q types and a current resistant to saturating
concentrations of dihydropyridine and neurotoxin antagonists. In this
study, we used whole-cell patch-clamp techniques to study the
effects of CRF on whole-cell Ca++ current
(ICa) in acutely dissociated CeA neurons and determine components of the current affected. CRF (1-400 nM) increased the peak
of the ICa in
50% of the CeA neurons recorded. In the
remaining neurons, CRF had little effect. The CRF-induced increase in
the ICa was concentration dependent and the estimated
EC50 value was 14.9 nM. CRF (50 nM) increased the peak
ICa by 25 ± 5% (n = 9). CRF
produced an increase in both the transient and the steady state current
but did not shift the peak of the current-voltage relationship. CRF did
not affect the voltage dependence of activation and inactivation, and
the CRF effect on ICas was not significantly different when
the neuron was held at
80 or
40 mV. The competitive CRF receptor
antagonist (
-helical CRF9-41, 3 µM) blocked the
CRF-induced increase in ICa, suggesting that the effect of CRF is receptor mediated. CRF (50 nM) enhanced the ICa
(20 ± 3%) in the presence of saturating concentrations of the
L-type blocker nimodipine and neurotoxin N- and Q-type blockers
-conotoxin GVIA and
-conotoxin MVIIC. We conclude that CRF
increased, through a receptor mechanism, dihydropyridine- and
neurotoxin-resistant current(s) in CeA neurons.
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