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Vol. 284, Issue 1, 170-179, 1998

Corticotropin-Releasing Factor Increases Dihydropyridine- and Neurotoxin-Resistant Calcium Currents in Neurons of the Central Amygdala

Baojian Yu and Patricia Shinnick-Gallagher

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 approx 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 (alpha -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 omega -conotoxin GVIA and omega -conotoxin MVIIC. We conclude that CRF increased, through a receptor mechanism, dihydropyridine- and neurotoxin-resistant current(s) in CeA neurons.


0022-3565/98/2841-0170$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics



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