Park M K, Bae Y M, Lee S H, Ho W K, Earm Y E
Department of Physiology and Biophysics, Seoul National University College of Medicine, 28 Yonkeun-Dong, Chongno-Ku, Seoul, 110-799, Korea.
Pflugers Arch. 1997 Nov;434(6):764-71. doi: 10.1007/s004240050463.
It has been suggested that hypoxic pulmonary vasoconstriction (HPV) results from the depolarization that is induced by the suppression of K+ current in pulmonary arterial smooth muscle cells (PASMC). We tested the hypothesis that the effect of the cellular redox potential on voltage-sensitive K+ (Kv) current is involved in HPV as a primary sensing mechanism. Kv current in PASMC and ear arterial smooth muscle cells (EASMC) of the rabbit was recorded using the whole-cell patch-clamp technique, and the effect of redox agents [dithiothreitol, DTT and 2,2'-dithio-bis(5-nitropyridine), DTBNP] was tested. Kv current was decreased by DTT, but increased by DTBNP. DTT accelerated the inactivation kinetics, but did not affect steady-state activation and inactivation, whereas DTBNP accelerated activation kinetics. Kv current has a non-inactivating window in the range of from -40 mV to +10 mV. The resting membrane potential measured using the nystatin-perforated-patch method, however, lay between -50 mV and -30 mV and was not depolarized by 5 mM 4-aminopyridine. The membrane-impermeable oxidizing agent DTNB has no effect on Kv current, suggesting that redox modulation sites are intracellular sulphydryl groups. In EASMC, Kv current was decreased by DTT, but increased by DTBNP, indicating that the redox-potential-induced modulation of Kv current in EASMC and in PASMC is the same. It is therefore concluded that Kv current is modulated by the cellular redox potential, but that this modulation is not involved in HPV as a primary sensing mechanism.
有人提出，缺氧性肺血管收缩（HPV）是由肺动脉平滑肌细胞（PASMC）中钾离子电流受抑制所诱导的去极化引起的。我们检验了这样一个假说，即细胞氧化还原电位对电压敏感性钾离子（Kv）电流的影响作为一种主要的传感机制参与了HPV过程。采用全细胞膜片钳技术记录兔PASMC和耳动脉平滑肌细胞（EASMC）中的Kv电流，并测试了氧化还原试剂[二硫苏糖醇（DTT）和2,2'-二硫双（5-硝基吡啶）（DTBNP）]的作用。DTT使Kv电流减小，而DTBNP使其增大。DTT加速了失活动力学，但不影响稳态激活和失活，而DTBNP加速了激活动力学。Kv电流在-40 mV至+10 mV范围内有一个非失活窗口。然而，使用制霉菌素穿孔膜片法测得的静息膜电位在-50 mV至-30 mV之间，并且未被5 mM 4-氨基吡啶去极化。膜不可渗透的氧化剂5,5'-二硫代双（2-硝基苯甲酸）（DTNB）对Kv电流无影响，表明氧化还原调节位点是细胞内的巯基。在EASMC中，DTT使Kv电流减小，而DTBNP使其增大，这表明EASMC和PASMC中氧化还原电位诱导的Kv电流调节是相同的。因此得出结论，Kv电流受细胞氧化还原电位调节，但这种调节作为一种主要传感机制不参与HPV过程。
