Petkov G V, Fusi F, Saponara S, Gagov H S, Sgaragli G P, Boev K K
Department of Pharmacology, University of Vermont, College of Medicine, Burlington, VT, USA.
Acta Physiol Scand. 2001 Nov;173(3):257-65. doi: 10.1046/j.1365-201X.2001.00907.x.
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)).
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。
