Ohya Y, Abe I, Fujii K, Takata Y, Fujishima M
Second Department of Internal Medicine, Kyushu University, Faculty of Medicine, Fukuoka, Japan.
Circ Res. 1993 Dec;73(6):1090-9. doi: 10.1161/01.res.73.6.1090.
Alterations in voltage-dependent Ca2+ channels in the arterial smooth muscle cells of spontaneously hypertensive rats (SHR) were investigated using the whole-cell voltage clamp and compared with Wistar-Kyoto (WKY) rats. Single cells were freshly isolated from resistance mesenteric arteries from 4- to 5-week-old (young) and 16- to 18-week-old (adult) SHR. Elevated blood pressure was only evident in adult SHR, not in young SHR. In young rats, the Ca2+ channel current density (current amplitude normalized by cell capacitance) was significantly higher (P < .01) in SHR than in WKY rats at the command potential of -10 mV or higher (with 50 mmol/L Ba2+): The current density at 20 mV was -16.8 +/- 1.1 pA/pF in SHR (n = 38 cells) and -11.0 +/- 0.8 pA/pF in WKY rats (n = 30 cells). In adult rats, the difference in current densities disappeared: -15.9 +/- 1.3 pA/pF in SHR (n = 25 cells) and -15.6 +/- 1.5 pA/pF in WKY rats (n = 29 cells). The ratio of maximal amplitude of T-type current to that of L-type current was low in young SHR (0.10 +/- 0.01) compared with the other three groups (0.16 to 0.20). Neither the activation curve nor the steady-state inactivation curve of SHR was different from that of age-matched WKY rats. However, the activation curves in adult rats were shifted to a hyperpolarized direction compared with those of young rats in both strains. These results suggest that the increased activity of voltage-dependent L-type Ca2+ channels of resistance arteries in young SHR may be related to the development of hypertension. The changes observed in adult rats may be due to a secondary modification of the channel during maturation and the presence of hypertension.
采用全细胞膜片钳技术研究自发性高血压大鼠(SHR)动脉平滑肌细胞中电压依赖性Ca2+通道的变化,并与Wistar-Kyoto(WKY)大鼠进行比较。从4至5周龄(幼年)和16至18周龄(成年)的SHR的阻力肠系膜动脉中新鲜分离出单细胞。血压升高仅在成年SHR中明显,幼年SHR中不明显。在幼年大鼠中,在-10 mV或更高的指令电位(含50 mmol/L Ba2+)下,SHR的Ca2+通道电流密度(电流幅度通过细胞电容归一化)显著高于WKY大鼠(P <.01):20 mV时的电流密度在SHR中为-16.8±1.1 pA/pF(n = 38个细胞),在WKY大鼠中为-11.0±0.8 pA/pF(n = 30个细胞)。在成年大鼠中,电流密度的差异消失:SHR中为-15.9±1.3 pA/pF(n = 25个细胞),WKY大鼠中为-15.6±1.5 pA/pF(n = 29个细胞)。与其他三组(0.16至0.20)相比,幼年SHR中T型电流最大幅度与L型电流最大幅度之比低(0.10±0.01)。SHR的激活曲线和稳态失活曲线与年龄匹配的WKY大鼠的曲线均无差异。然而,与两种品系的幼年大鼠相比,成年大鼠的激活曲线均向超极化方向偏移。这些结果表明,幼年SHR中阻力动脉电压依赖性L型Ca2+通道活性增加可能与高血压的发生发展有关。成年大鼠中观察到的变化可能是由于通道在成熟过程中的继发性修饰以及高血压的存在。