Selective enhancement of l-type calcium currents by corticotropin in acutely isolated rat amygdala neurons.
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 approximately 75% and approximately 50%, respectively. Nimodipine (1 microM) reduced the I(Ca) by approximately 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 omega-conotoxin-GVIA and omega-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 Ca(2+) currents in brain neurons and that this increase is mediated through L-type channels and involves a cAMP-dependent mechanism.
Young
C
C
Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan.
Huang
Y
Y
Lin
C
C
Shen
Y
Y
Gean
P
P
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D020746:Calcium Channels, L-Type; D000324:Adrenocorticotropic Hormone; D017868:Cyclic AMP-Dependent Protein Kinases