Franco-Obregón A, López-Barneo J
Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Seville, Spain.
Am J Physiol. 1996 Dec;271(6 Pt 2):H2290-9. doi: 10.1152/ajpheart.1996.271.6.H2290.
We studied the effect of O2 tension (PO2) on the activity of voltage-gated Ca2+ channels recorded in whole cell patch-clamped smooth muscle cells enzymatically dispersed from rabbit cerebral, celiac, femoral, and main pulmonary arteries, as well as from the porcine coronary artery. In all myocyte classes examined, a reduction of PO2 (hypoxia) produced a rapid and reversible inhibition of the macroscopic L-type Ca2+ current of similar general characteristics. The hypoxic inhibition of Ca2+ channel activity closely followed the time course of bath exchange, first becoming apparent at below approximately 80 mmHg PO2. The interaction of O2 with the Ca2+ channels was strongly voltage dependent. At -30 mV the average extent of current inhibition was approximately 80%; however, no effect or even potentiation of current amplitude was observed at potentials more positive than +30 mV. Hypoxia selectively slowed activation kinetics (approximately 1.5 times at -20 mV); however, channel deactivation and inactivation were unaltered by low PO2. In addition, hypoxia produced a reversible shift (8.1 +/- 1.0 mV, n = 12) of the Ca2+ conductance-voltage curve toward positive membrane potentials. We propose that the O2 sensitivity of Ca2+ channels may contribute to the well-known hypoxic dilatation of systemic and the main pulmonary arteries.
我们研究了氧分压（PO₂）对全细胞膜片钳记录的电压门控Ca²⁺通道活性的影响，这些通道来自酶解分散的兔脑动脉、腹腔动脉、股动脉和主肺动脉以及猪冠状动脉的平滑肌细胞。在所有检测的心肌细胞类型中，PO₂降低（缺氧）会迅速且可逆地抑制宏观L型Ca²⁺电流，其一般特征相似。Ca²⁺通道活性的缺氧抑制与浴液交换的时间进程密切相关，在PO₂低于约80 mmHg时首先明显出现。O₂与Ca²⁺通道的相互作用强烈依赖电压。在-30 mV时，电流抑制的平均程度约为80%；然而，在高于+30 mV的电位下未观察到电流幅度的影响甚至增强。缺氧选择性地减慢激活动力学（在-20 mV时约为1.5倍）；然而，低PO₂对通道失活和去激活没有影响。此外，缺氧使Ca²⁺电导-电压曲线向正膜电位发生可逆性偏移（8.1±1.0 mV，n = 12）。我们提出，Ca²⁺通道的O₂敏感性可能有助于众所周知的全身和主肺动脉的缺氧性扩张。
