Vol. 59, Issue 3, 604-611, March 2001

Selective Enhancement of L-Type Calcium Currents by Corticotropin in Acutely Isolated Rat Amygdala Neurons

Chainllie Young, Ya-Chun Huang, Chih-Hung Lin, Yu-Zen Shen, and Po-Wu Gean

Department of Pediatrics, College of Medicine, National Taiwan University, Taipei (C.Y.,Y.-Z.S.); and Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan (Y.-C.H., C.-H.L., P.-W.G.)

The modulation of voltage-dependent calcium currents (I_Ca) by corticotropin was studied in acutely dissociated rat amygdala neurons using whole-cell, patch-clamp recording techniques. Application of corticotropin_1-24 or corticotropin_4-10 increased I_Ca 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 I_Ca by ~30%. Subsequent application of corticotropin in the presence of nimodipine failed to produce an enhancement of I_Ca, suggesting that corticotropin acts selectively on L-type channels. In addition, corticotropin-mediated enhancement of I_Ca after exposure to -conotoxin-GVIA and -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 (S_p)-cyclic adenosine 3',5'-monophosphothioate [(S_p)-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 (R_p)-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.