Corticotropin-releasing factor increases dihydropyridine- and neurotoxin-resistant calcium currents in neurons of the central amygdala.
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 approximately 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 microM) 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.
Yu
B
B
Department of Pharmacology and Toxicology, University of Texas Medical Branch at Galveston, USA.
Shinnick-Gallagher
P
P
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009498:Neurotoxins; D003346:Corticotropin-Releasing Hormone; D002118:Calcium