The modulation of voltage-dependent calcium currents (lca) by corticotropin was studied in acutely dissociated rat amygdala neurons using whole-cell, patch-clamp recording techniques. Application of corticotropin1-24 or corticotropin4-10 increased lCa in a concentration-dependent manner, with half-maximal effective concentrations of 65 and 176 nM and maximal increases of ∼75% and ∼50%, respectively. Nimodipine (1 μM) reduced the lCa by ∼30%. Subsequent application of corticotropin in the presence of nimodipine failed to produce an enhancement of lCa, suggesting that corticotropin acts selectively on L-type channels. In addition, corticotropin-mediated enhancement of lCa after exposure to ω-conotoxin-GVIA and ω-agatoxin-IV was not significantly different from that observed in the control neurons, ruling out the involvement of N- and P/Q-type channels. The effect of corticotropin was mimicked by forskolin and (Sp)-cyclic adenosine 3′,5′-monophosphothioate [(Sp)-cAMPS] and was significantly enhanced in the presence of phosphodiesterase or protein phosphatase inhibitors. On the other hand, the effect of corticotropin was markedly reduced in neurons intracellularly dialyzed with (Rp)-cAMPS, a regulatory site antagonist of cAMP-dependent protein kinase (PKA) or by extracellular perfusion of KT 5720, a catalytic site antagonist of PKA. Taken together, these results show for the first time that corticotropin enhances voltage-dependent Ca2+ currents in brain neurons and that this increase is mediated through L-type channels and involves a cAMP-dependent mechanism.
All Science Journal Classification (ASJC) codes
- Molecular Medicine