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, wi...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Molecular pharmacology 2001-03, Vol.59 (3), p.604-611
Hauptverfasser: Young, C, Huang, Y, Lin, C, Shen, Y, Gean, P
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
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 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 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 Ca 2+ currents in brain neurons and that this increase is mediated through L-type channels and involves a cAMP-dependent mechanism.
ISSN:0026-895X
1521-0111
DOI:10.1124/mol.59.3.604