Lee S H, Ho W K, Earm Y E
Department of Physiology and Heart Research Institute, Seoul National University College of Medicine, 28 Yonkeun-Dong, Chongno-Ku, Seoul, 110 799, Korea.
Exp Physiol. 1998 Nov;83(6):707-15. doi: 10.1113/expphysiol.1998.sp004152.
Hypoxic pulmonary vasoconstriction (HPV) is an important mechanism for matching the ventilation/perfusion ratio in the lung, but the signal transduction pathway through which hypoxia induces vasoconstriction remains unclear. We hypothesized that the decrease in K+ current induced by hypoxia is a key mechanism for HPV, and examined the effects of the substances which are expected to accumulate during hypoxia on the activity of large conductance Ca2+-activated K+ (BKCa) channels. Pulmonary and ear arterial smooth muscle cells were isolated from the rabbit using enzymatic digestion, and large conductance Ca2+-activated K+ current (IBK,Ca) was recorded in symmetrical K+ concentrations using the inside-out mode of the patch-clamp technique. Increasing the Na+ concentration on the intracellular side suppressed IBK,Ca dose dependently: 4.6, 20.9, 35.5 and 44.6 % reduction with 4, 8, 12 and 16 mM Na+, respectively. Mg2+ also reduced IBK,Ca, and the maximum reduction was obtained at 0.5 mM. Lactate, adenosine, ADP and ATP did not significantly affect IBK,Ca. There was no difference between pulmonary and ear arterial smooth muscle cells in their response to the above substances; this finding rules out modulation of BKCa channels by the various factors thought to accumulate during hypoxia as a major mechanism involved in the decrease in the K+ conductance of pulmonary arteries in hypoxia.
缺氧性肺血管收缩（HPV）是肺通气/血流比值匹配的重要机制，但缺氧诱导血管收缩的信号转导途径仍不清楚。我们推测缺氧诱导的K+电流降低是HPV的关键机制，并研究了缺氧时可能蓄积的物质对大电导Ca2+激活K+（BKCa）通道活性的影响。采用酶消化法从兔分离出肺动脉和耳动脉平滑肌细胞，运用膜片钳技术的内面向外模式，在对称K+浓度下记录大电导Ca2+激活K+电流（IBK,Ca）。增加细胞内侧的Na+浓度可剂量依赖性抑制IBK,Ca：分别用4、8、12和16 mM Na+时，抑制率分别为4.6%、20.9%、35.5%和44.6%。Mg2+也可降低IBK,Ca，在0.5 mM时降低幅度最大。乳酸、腺苷、ADP和ATP对IBK,Ca无显著影响。肺动脉和耳动脉平滑肌细胞对上述物质的反应无差异；这一发现排除了缺氧时被认为会蓄积的各种因素对BKCa通道的调节作用，而这种调节作用是缺氧时肺动脉K+电导降低的主要机制。
