Zhang Yongde, Gao Yu-Jing, Zuo Jianmin, Lee Robert M K W, Janssen Luke J
Department of Medicine, McMaster University, Canada.
Eur J Pharmacol. 2005 May 9;514(2-3):111-9. doi: 10.1016/j.ejphar.2005.03.032.
We investigated K+ currents and their regulation by the sarcoplasmic reticulum in mesenteric arterial smooth muscle cells of the spontaneously hypertensive rat (SHR). Using perforated patch-clamp technique, we found the overall K+ current density was significantly lower in adult SHR compared to adult Wistar-Kyoto rats (WKY). The K+ currents were almost exclusively of large-conductance Ca2+-dependent (BK(Ca)) variety in SHR, but largely of voltage-gated (Kv) variety in WKY. Western blot assay showed parallel findings. These differences were not observed in pre-hypertensive rats. Depleting the intracellular Ca2+ store inhibited the K+ currents in adult SHR. Ryanodine augmented the K+ current at 1 microM, but suppressed it at 10 microM; 2-aminoethoxydiphenyl borate demonstrated concentration-dependent inhibition. We conclude that an alteration of membrane K+ channel composition has resulted in lower overall K+ current density. The changes in K+ current type may indicate an underlying defect in Ca2+-handling that predisposes smooth muscle cells to the hypertensive phenotype.
我们研究了自发性高血压大鼠（SHR）肠系膜动脉平滑肌细胞中的钾离子电流及其受肌浆网的调节。使用穿孔膜片钳技术，我们发现成年SHR的总体钾离子电流密度显著低于成年Wistar-Kyoto大鼠（WKY）。在SHR中，钾离子电流几乎完全是大电导钙依赖性（BK(Ca)）类型，但在WKY中主要是电压门控（Kv）类型。蛋白质印迹分析显示了类似的结果。在高血压前期大鼠中未观察到这些差异。耗尽细胞内钙库会抑制成年SHR的钾离子电流。Ryanodine在1微摩尔时增强钾离子电流，但在10微摩尔时抑制它；2-氨基乙氧基二苯硼酸盐表现出浓度依赖性抑制。我们得出结论，膜钾离子通道组成的改变导致了总体钾离子电流密度降低。钾离子电流类型的变化可能表明钙处理存在潜在缺陷，使平滑肌细胞易患高血压表型。
