Selective Enhancement of L-Type Calcium Currents by Corticotropin in Acutely Isolated Rat Amygdala Neurons
- 1Department of Pediatrics, College of Medicine, National Taiwan University, Taipei (C.Y.,Y.-Z.S.); and 2Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan (Y.-C.H., C.-H.L., P.-W.G.)
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 (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.
Footnotes
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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.
- Abbreviations:
- HPA
- hypothalamus-pituitary-adrenal
- POMC
- pro-opiomelanocortin
- VDCCs
- voltage-dependent Ca2+channels
- PIPES
- 1,4-piperazine(ethanesulfonic acid
- TEA
- tetraethylammonium hydrochloride
- ω-CgTX
- ω-conotoxin-GVIA
- ω-AgTX
- ω-agatoxin-IV
- TTX
- tetrodotoxin
- I-V
- current-voltage
- PKA
- cAMP-dependent protein kinase
- cAMPS
- cyclic adenosine 3′,5′-monophosphothioate
- IBMX
- isobutylmethylxanthine
- PP
- protein phosphatase
- MC
- melanocortin
- L-LTP
- long-lasting potentiation
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- Received August 15, 2000.
- Accepted November 22, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
