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WKY和SHR胸主动脉新鲜分离的心肌细胞中钾离子通道特性的比较。

Comparison of K+ channel properties in freshly isolated myocytes from thoracic aorta of WKY and SHR.

作者信息

Cox R H

机构信息

Bockus Research Institute, Graduate Hospital, Philadelphia, PA 19146.

出版信息

Am J Hypertens. 1996 Sep;9(9):884-94. doi: 10.1016/s0895-7061(96)00179-3.

Abstract

Altered function of smooth muscle cell K+ channels have been reported in hypertension, but the contribution of various K+ channel types to these changes has not been completely determined. The purpose of this study was to compare the contribution of K+ channel types to whole cell K+ currents recorded from isolated thoracic aorta myocytes of 13 to 15 week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Cells were isolated by collagenase and elastase digestion, and K+ currents recorded using whole cell voltage clamp methods at room temperature. Cells were superfused with a solution containing (in mmol/ L) 140 NaCl, 5 KCl, 2 CaCl2, 1 MgCl2, 10 HEPES, and 10 glucose. Pipettes were filled with a solution containing (in mmol/L) 120 KCl, 5 NaCl, 5 MgATP, 20 HEPES, and 10 BAPTA. The K+ currents (IK) recorded from a holding potential (HP) of -80 mV were smaller in the SHR compared to those in WKY (for example, at 20 mV: WKY = 6.1 +/- 0.6 pA/pF and SHR = 3.7 +/- 0.2 pA/pF). Values of cell capacitance were not different between the two groups (WKY = 25.2 +/- 3.2 pF and SHR = 26.6 +/- 1.9 pF). A component of IK inhibited by voltage (Kv) over the range from -80 to -20 mV was smaller in SHR. The voltage dependence of Kv availability and activation were not significantly different between the two groups. IK recorded from a HP = -20 mV (KCa) was not different between the two groups. Difference currents calculated from IK measured at HP of -80 and -20 mV (that is, Kv) were smaller in SHR as was the fraction of IK inhibited by 4-aminopyridine. These results suggest that under conditions of low intracellular [Ca2+] there are no differences in KCa currents, but the Kv currents are smaller in SHR. Inhibition of Kv by 4-aminopyridine (0.1 to 10 mmol/L) caused larger increases in basal tone in WKY aorta. These results suggest that Kv channels contribute to resting K+ conductance in both WKY and SHR aorta, but with a relatively larger contribution in the WKY.

摘要

已有报道称高血压患者平滑肌细胞钾通道功能发生改变,但尚未完全确定各种类型钾通道对这些变化的作用。本研究的目的是比较不同类型钾通道对13至15周龄Wistar-Kyoto(WKY)大鼠和自发性高血压大鼠(SHR)离体胸主动脉肌细胞记录的全细胞钾电流的作用。通过胶原酶和弹性蛋白酶消化分离细胞,并在室温下使用全细胞电压钳方法记录钾电流。用含有(以mmol/L计)140 NaCl、5 KCl、2 CaCl2、1 MgCl2、10 HEPES和10葡萄糖的溶液对细胞进行灌流。移液管中填充含有(以mmol/L计)120 KCl、5 NaCl、5 MgATP、20 HEPES和10 BAPTA的溶液。与WKY大鼠相比,SHR大鼠从-80 mV的钳制电位(HP)记录的钾电流(IK)较小(例如,在20 mV时:WKY = 6.1±0.6 pA/pF,SHR = 3.7±0.2 pA/pF)。两组之间的细胞电容值无差异(WKY = 25.2±3.2 pF,SHR = 26.6±1.9 pF)。在-80至-20 mV范围内受电压(Kv)抑制的IK成分在SHR中较小。两组之间Kv可用性和激活的电压依赖性无显著差异。从HP = -20 mV记录的IK(KCa)在两组之间无差异。从在HP为-80和-20 mV时测量的IK计算的差异电流(即Kv)在SHR中较小,4-氨基吡啶抑制的IK分数也是如此。这些结果表明,在细胞内[Ca2+]较低的情况下,KCa电流无差异,但SHR中的Kv电流较小。4-氨基吡啶(0.1至10 mmol/L)对Kv的抑制导致WKY主动脉基础张力的更大增加。这些结果表明,Kv通道对WKY和SHR主动脉的静息钾电导均有贡献,但在WKY中贡献相对较大。

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