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17β-雌二醇减弱A7r5血管平滑肌细胞系中的电压依赖性Ca2+电流。

17 beta-Estradiol attenuates voltage-dependent Ca2+ currents in A7r5 vascular smooth muscle cell line.

作者信息

Zhang F, Ram J L, Standley P R, Sowers J R

机构信息

Department of Medicine, School of Medicine, Wayne State University, Detroit, Michigan 48201.

出版信息

Am J Physiol. 1994 Apr;266(4 Pt 1):C975-80. doi: 10.1152/ajpcell.1994.266.4.C975.

Abstract

Previous studies have shown that 17 beta-estradiol (beta-E2) has a direct acute inhibitory effect on vascular smooth muscle (VSM) contraction. To investigate the mechanisms underlying this phenomenon, we utilized whole cell patch-clamping techniques to study effects of beta-E2 on voltage-dependent Ca2+ channels in cultured VSM cells (VSMC). T- and L-type Ca2+ currents were characterized with ramp and pulse protocols in A7r5 cultured VSMC. T-type current, inactivated in < 100 ms, was reduced by Ba2+ and was comparatively little affected by isradipine. L-type current required higher voltages to activate, inactivated slowly, was greatly increased by Ba2+, and could be completely inhibited by 5 microM isradipine. beta-E2 (10 microM) significantly reduced peak L-type Ba2+ current and T-type Ca2+ current within 1-2 min, whereas alpha E2 (a hormonally inactive isomer of estradiol) caused significantly less reduction in both types of current. Vehicle (0.1% ethanol) had no significant effect on either current. The inhibitory effect of beta-E2 on voltage-dependent Ca2+ currents may contribute to previously demonstrated beta-E2 attenuation of VSM contraction.

摘要

先前的研究表明,17β-雌二醇(β-E2)对血管平滑肌(VSM)收缩具有直接的急性抑制作用。为了研究这一现象背后的机制,我们利用全细胞膜片钳技术来研究β-E2对培养的血管平滑肌细胞(VSMC)中电压依赖性Ca2+通道的影响。在A7r5培养的VSMC中,通过斜坡和脉冲方案对T型和L型Ca2+电流进行了表征。T型电流在<100毫秒内失活,被Ba2+降低,并且相对受异搏定的影响较小。L型电流需要更高的电压来激活,失活缓慢,被Ba2+大大增加,并且可以被5μM异搏定完全抑制。β-E2(10μM)在1-2分钟内显著降低了L型Ba2+电流和T型Ca2+电流的峰值,而α-E2(雌二醇的一种激素无活性异构体)对两种电流的降低作用明显较小。载体(0.1%乙醇)对两种电流均无显著影响。β-E2对电压依赖性Ca2+电流的抑制作用可能有助于先前证明的β-E2对VSM收缩的减弱作用。

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