Preferential inhibition of L- and N-type calcium channels in the rat hippocampal neurons by cilnidipine.
The effect of a dihydropyridine Ca2+ antagonist, cilnidipine, on voltage-dependent Ca2+ channels was studied in acutely dissociated rat CA1 pyramidal neurons using the nystatin-perforated patch recording configuration under voltage-clamp conditions. Cilnidipine had no effect on low-voltage-activated (LVA) Ca2+ channels at the low concentrations under 10(-6) M. On the other hand, cilnidipine inhibited the high-voltage-activated (HVA) Ca2+ current (I(Ca)) in a concentration-dependent manner and the inhibition curve showed a step-wise pattern; cilnidipine selectively reduced only L-type HVA I(Ca) at the low concentrations under 10(-7) and 10(-6) M cilnidipine blocked not only L- but also N-type HVA I(Ca). At the high concentration over 10(-6) M cilnidipine non-selectively blocked the T-type LVA and P/Q- and R-type HVA Ca2+ channels. This is the first report that cilnidipine at lower concentration of 10(-6) M blocks both L-and N-type HVA I(Ca) in the hippocampal neurons.
Murai
Y
Y
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Uneyama
H
H
Ishibashi
H
H
Takahama
K
K
Akaike
N
N
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D020864:Calcium Channels, N-Type / Q000187:drug effects* / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; C065927:cilnidipine