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.