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 1â24 or corticotropin 4â10 increased I Ca in a concentration-dependent manner, wi...
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Veröffentlicht in: | Molecular pharmacology 2001-03, Vol.59 (3), p.604-611 |
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Zusammenfassung: | 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 1â24 or corticotropin 4â10 increased I Ca in a concentration-dependent manner, with half-maximal effective concentrations of 65 and 176 nM and maximal increases of
â¼75% and â¼50%, respectively. Nimodipine (1 μM) reduced the I Ca by â¼30%. 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 Ï-conotoxin-GVIA and Ï-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 3â²,5â²-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. |
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ISSN: | 0026-895X 1521-0111 |
DOI: | 10.1124/mol.59.3.604 |