氨氯地平对克隆的N型钙离子通道的电压和pH依赖性阻滞

Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine.

Furukawa T, Nukada T, Suzuki K, Fujita Y, Mori Y, Nishimura M, Yamanaka M

First Department of Internal Medicine, Teikyo University, Itabashi-ku, Tokyo, Japan.

Br J Pharmacol. 1997 Jul;121(6):1136-40. doi: 10.1038/sj.bjp.0701226.

Abstract

Two types of Ca2+ channel alpha1-subunits were co-expressed in Xenopus oocytes with the Ca2+ channel alpha2- and beta1-subunits. The Ba2+ current through the alpha1C alpha2beta and the alpha1B alpha2beta channels had electrophysiological and pharmacological properties of L- and N-type Ca2+ channels, respectively. 2. Amlodipine had a strong blocking action on both the L-type and N-type Ca2+ channels expressed in the oocyte. The potency of the amlodipine block on the N-type Ca2+ channel was comparable to that on the L-type Ca2+ channel. At -100 mV holding potential, the IC50 values for amlodipine block on the L-type and N-type Ca2+ channel were 2.4 and 5.8 microM, respectively. 3. The blocking action of amlodipine on the N-type Ca2+ channel was dependent on holding potential and extracellular pH, as has been observed with amlodipine block on the L-type Ca2+ channel. A depolarized holding potential and high pH enhanced the blocking action of amlodipine. 4. The time course of block development by amlodipine was similar for L-type and N-type Ca2+ channels. However, it was slower than the time course of block development by nifedipine for the L-type Ca2+ channel.

摘要

两种类型的Ca2+通道α1亚基与Ca2+通道α2和β1亚基在非洲爪蟾卵母细胞中共表达。通过α1Cα2β和α1Bα2β通道的Ba2+电流分别具有L型和N型Ca2+通道的电生理和药理学特性。2. 氨氯地平对卵母细胞中表达的L型和N型Ca2+通道均有强烈的阻断作用。氨氯地平对N型Ca2+通道的阻断效力与对L型Ca2+通道的相当。在-100 mV的钳制电位下，氨氯地平对L型和N型Ca2+通道的IC50值分别为2.4和5.8 microM。3. 氨氯地平对N型Ca2+通道的阻断作用依赖于钳制电位和细胞外pH，这与氨氯地平对L型Ca2+通道的阻断作用所观察到的情况相同。去极化的钳制电位和高pH增强了氨氯地平的阻断作用。4. 氨氯地平对L型和N型Ca2+通道的阻断发展时间进程相似。然而，它比硝苯地平对L型Ca2+通道的阻断发展时间进程要慢。