西尼地平对大鼠海马神经元中L型和N型钙通道的优先抑制作用。

Preferential inhibition of L- and N-type calcium channels in the rat hippocampal neurons by cilnidipine.

作者信息

Murai Y, Uneyama H, Ishibashi H, Takahama K, Akaike N

机构信息

Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

出版信息

Brain Res. 2000 Jan 31;854(1-2):6-10. doi: 10.1016/s0006-8993(99)02295-7.

DOI:10.1016/s0006-8993(99)02295-7

PMID:10784100

Abstract

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.

摘要

在电压钳制条件下，采用制霉菌素穿孔膜片钳记录模式，在急性分离的大鼠CA1锥体神经元中研究了二氢吡啶类钙离子拮抗剂西尼地平对电压依赖性钙离子通道的作用。在浓度低于10^(-6) M时，西尼地平对低电压激活（LVA）钙离子通道无影响。另一方面，西尼地平以浓度依赖性方式抑制高电压激活（HVA）钙离子电流（I(Ca)），且抑制曲线呈阶梯状；在浓度低于10^(-7) M时，西尼地平仅选择性降低L型HVA I(Ca)，而在10^(-6) M时，西尼地平不仅阻断L型，还阻断N型HVA I(Ca)。在浓度高于10^(-6) M时，西尼地平非选择性地阻断T型LVA以及P/Q型和R型HVA钙离子通道。这是首次报道在较低浓度10^(-6) M时，西尼地平可阻断海马神经元中的L型和N型HVA I(Ca)。