Cox R H, Lozinskaya I M
Bockus Research Institute, Graduate Hospital, Philadelphia, PA 19146, USA.
Hypertension. 1995 Dec;26(6 Pt 2):1060-4. doi: 10.1161/01.hyp.26.6.1060.
The greater efficacy of organic channel blockers in lowering peripheral resistance and blood pressure in hypertensive subjects has been suggested to be the result of augmented calcium influx through L-type calcium channels in arterial smooth muscle. These studies were performed to determine whether differences exist in voltage-gated calcium channels of mesenteric artery branches from 20-week-old spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). Single myocytes were acutely isolated by collagenase and elastase treatment and studied at room temperature (approximately 20 degrees C) with the use of whole-cell, patch-clamp methods. Maximum values of calcium current measured at 0 mV from a holding potential of -90 mV were larger in SHR myocytes (105 +/- 11 versus 149 +/- 15 pA). Values of cell capacitance were smaller in SHR (29.5 +/- 1.3 pF) compared with WKY (35.0 +/- 1.5 pF) myocytes. Cell capacitance measures surface membrane area and, when used to normalize calcium currents, magnified the difference between WKY and SHR to approximately 47%. There was a larger percent reduction of maximum calcium current at holding potentials of -60 and -40 mV in SHR compared with WKY myocytes: for example, at -40 mV calcium current was reduced from values at -90 mV by -73 +/- 2% in SHR compared with -58 +/- 1% in WKY. When divided by the maximum current for each holding potential, the voltage dependence of normalized calcium currents for the two groups was completely superimposed. Difference currents were calculated by subtracting currents measured from holding potentials of -90 and -40 mV. The voltage dependence of difference currents was identical to that of the calcium currents measured from the two values of holding potential.(ABSTRACT TRUNCATED AT 250 WORDS)
有机通道阻滞剂在降低高血压患者外周阻力和血压方面具有更高的疗效,这被认为是由于动脉平滑肌中通过L型钙通道的钙内流增加所致。进行这些研究是为了确定20周龄自发性高血压大鼠(SHR)与Wistar-Kyoto大鼠(WKY)相比,肠系膜动脉分支的电压门控钙通道是否存在差异。通过胶原酶和弹性蛋白酶处理急性分离单个心肌细胞,并在室温(约20摄氏度)下使用全细胞膜片钳方法进行研究。在-90 mV的 holding 电位下,在0 mV处测量的钙电流最大值在SHR心肌细胞中更大(105±11对149±15 pA)。与WKY(35.0±1.5 pF)心肌细胞相比,SHR(29.5±1.3 pF)的细胞电容值更小。细胞电容测量表面膜面积,当用于标准化钙电流时,放大了WKY和SHR之间的差异至约47%。与WKY心肌细胞相比,SHR在-60和-40 mV的 holding 电位下最大钙电流的降低百分比更大:例如,在-40 mV时,SHR的钙电流从-90 mV时的值降低了-73±2%,而WKY为-58±1%。当除以每个 holding 电位的最大电流时,两组标准化钙电流的电压依赖性完全重叠。通过减去从-90和-40 mV的 holding 电位测量的电流来计算差异电流。差异电流的电压依赖性与从两个 holding 电位值测量的钙电流的电压依赖性相同。(摘要截断于250字)