Abstract
The modulation of voltage-dependent calcium currents (ICa) by corticotropin was studied in acutely dissociated rat amygdala neurons using whole-cell, patch-clamp recording techniques. Application of corticotropin1–24 or corticotropin4–10increased ICa 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 ICa by ∼30%. Subsequent application of corticotropin in the presence of nimodipine failed to produce an enhancement of ICa, suggesting that corticotropin acts selectively on L-type channels. In addition, corticotropin-mediated enhancement of ICa 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 (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.
Footnotes
- Received August 15, 2000.
- Accepted November 22, 2000.
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Send reprint requests to: Dr. Po-Wu Gean, Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan 701. E-mail: powu{at}mail.ncku.edu.tw
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This study was supported by the National Science Council (NSC86–2314-B006–002-M10) and the Academic Excellence Program of the Ministry of Education (89-B-FA08–1-4) of Taiwan, Republic of China.
- The American Society for Pharmacology and Experimental Therapeutics
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