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大鼠尾主动脉新鲜分离平滑肌细胞中电压门控钙电流的特性分析。

Characterization of voltage-gated calcium currents in freshly isolated smooth muscle cells from rat tail main artery.

作者信息

Petkov G V, Fusi F, Saponara S, Gagov H S, Sgaragli G P, Boev K K

机构信息

Department of Pharmacology, University of Vermont, College of Medicine, Burlington, VT, USA.

出版信息

Acta Physiol Scand. 2001 Nov;173(3):257-65. doi: 10.1046/j.1365-201X.2001.00907.x.

Abstract

The aim of the present study was to characterize voltage-gated Ca2+ currents in smooth muscle cells freshly isolated from rat tail main artery in the presence of 5 mmol L(-1) external Ca2+. Calcium currents were identified on the basis of their voltage dependencies and sensitivity to nifedipine, Ni2+ and cinnarizine. In the majority of the cells studied, T- and L-type currents were observed, while the remaining cells showed predominantly L-type currents. In the latter group of cells, holding potential change from -50 to either -70 or -90 mV increased the corresponding inward current amplitude while its voltage activation threshold remained unchanged. The steady state inactivation of L-type Ca2+ channels showed half-maximal inactivation at -38 mV. A Ca2+-dependent inactivation was also evident. Nifedipine (3 micromol L(-1)) blocked L-type but not T-type Ca2+ currents. Ni2+ (50 micromol L(-1)) as well as cinnarizine (1 micromol L(-1)) suppressed the nifedipine-resistant, T-type component of the currents. At higher concentrations, both Ni2+ (0.3-1 mmol L(-1)) and cinnarizine (10 micromol L(-1)) blocked the net inward current. Replacement of Ca2+ with 10 mmol L(-)1 Ba2+ significantly increased the amplitude of L-type Ca2+ currents. These results demonstrate that smooth muscle cells freshly isolated from rat tail main artery may be divided into two populations, one expressing both L- and T-type and the other only L-type Ca2+ channels. Furthermore, this report shows that in arterial smooth muscle cells cinnarizine potently inhibited T-type currents at low concentrations (1 micromol L(-1)) but also blocked L-type Ca2+ currents at higher concentrations (10 micromol L(-1)).

摘要

本研究的目的是在存在5 mmol L⁻¹ 细胞外Ca²⁺ 的情况下,对从大鼠尾主动脉新鲜分离的平滑肌细胞中的电压门控Ca²⁺ 电流进行特性描述。钙电流是根据其电压依赖性以及对硝苯地平、Ni²⁺ 和桂利嗪的敏感性来确定的。在大多数所研究的细胞中,观察到了T型和L型电流,而其余细胞主要表现为L型电流。在后者这组细胞中,保持电位从 -50 mV变为 -70 mV或 -90 mV时,相应的内向电流幅度增加,而其电压激活阈值保持不变。L型Ca²⁺ 通道的稳态失活在 -38 mV时表现出半数最大失活。Ca²⁺ 依赖性失活也很明显。硝苯地平(3 μmol L⁻¹)阻断L型而非T型Ca²⁺ 电流。Ni²⁺(50 μmol L⁻¹)以及桂利嗪(1 μmol L⁻¹)抑制了电流中对硝苯地平耐药的T型成分。在较高浓度时,Ni²⁺(0.3 - 1 mmol L⁻¹)和桂利嗪(10 μmol L⁻¹)都阻断了净内向电流。用10 mmol L⁻¹ Ba²⁺ 替代Ca²⁺ 显著增加了L型Ca²⁺ 电流的幅度。这些结果表明,从大鼠尾主动脉新鲜分离的平滑肌细胞可分为两类,一类同时表达L型和T型Ca²⁺ 通道,另一类仅表达L型Ca²⁺ 通道。此外,本报告表明,在动脉平滑肌细胞中,桂利嗪在低浓度(1 μmol L⁻¹)时能有效抑制T型电流,但在高浓度(10 μmol L⁻¹)时也能阻断L型Ca²⁺ 电流。

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