Anwer K, Oberti C, Perez G J, Perez-Reyes N, McDougall J K, Monga M, Sanborn B M, Stefani E, Toro L
Department of Biochemistry, University of Texas Medical School at Houston.
Am J Physiol. 1993 Oct;265(4 Pt 1):C976-85. doi: 10.1152/ajpcell.1993.265.4.C976.
The role of Ca(2+)-activated potassium (KCa) channels in the regulation of membrane potential, intracellular free calcium ([Ca2+]i) and contraction was investigated in uterine smooth muscle and myometrial cells. In an immortalized human myometrial cell line, oxytocin increased [Ca2+]i and [3H]inositol phosphate formation. Relaxin attenuated the oxytocin-induced increase in [Ca2+]i. In cell-attached patches, membrane depolarization activated a large-conductance KCa channel (179 +/- 4 pS). Iberiotoxin (IbTX), a potent blocker of "maxi" KCa channels (A. Galvez, G. Gimenez-Gallego, J. P. Reuben, L. Roy-Contanciin, P. Feigenbaum, G. J. Kaczorowski, and M. L. Garcia. J. Biol. Chem. 265: 11083-11090, 1990) produced long closed events (approximately 6 min) in these channels. In agreement with this blockage, IbTX depolarized the cells by 9.8 +/- 2.8 mV and caused a dose-dependent increase in [Ca2+]i with a half-maximal effective concentration of 0.79 nM. IbTX also caused phasic contractions in human myometrial strips and increased both the frequency and force of spontaneous contractions in estrogen-primed rat myometrial strips. Moreover, myometrial contractility was also affected by 1 mM tetraethylammonium, a concentration that blocks uterine smooth muscle KCa channels when applied to the extracellular side (G. J. Perez, L. Toro, S. D. Erulkar, and E. Stefani. Am. J. Obstet. Gynecol. 168: 652-660, 1993). These results strongly suggest that the large conductance KCa channels may actively participate in the control of human myometrial cell membrane potential and [Ca2+].
研究了钙激活钾（KCa）通道在子宫平滑肌和子宫肌层细胞中对膜电位、细胞内游离钙（[Ca2+]i）及收缩的调节作用。在一种永生化的人子宫肌层细胞系中，催产素可增加[Ca2+]i及[3H]肌醇磷酸的生成。松弛素可减弱催产素诱导的[Ca2+]i升高。在细胞贴附膜片上，膜去极化激活了一种大电导KCa通道（179±4 pS）。艾比毒素（IbTX）是“大”KCa通道的强效阻断剂（A. 加尔韦斯、G. 希门尼斯 - 加列戈、J. P. 鲁本、L. 罗伊 - 孔坦西因、P. 费根鲍姆、G. J. 卡佐罗夫斯基和M. L. 加西亚。《生物化学杂志》265: 11083 - 11090, 1990），可使这些通道产生长时间关闭事件（约6分钟）。与这种阻断作用一致，IbTX使细胞去极化9.8±2.8 mV，并引起[Ca2+]i呈剂量依赖性增加，半数有效浓度为0.79 nM。IbTX还可引起人子宫肌条的阶段性收缩，并增加雌激素预处理的大鼠子宫肌条自发收缩的频率和力量。此外，1 mM四乙铵也会影响子宫肌层的收缩性，当应用于细胞外侧时，该浓度可阻断子宫平滑肌KCa通道（G. J. 佩雷斯、L. 托罗、S. D. 埃鲁卡尔和E. 斯特凡尼。《美国妇产科杂志》168: 652 - 660, 1993）。这些结果强烈表明，大电导KCa通道可能积极参与对人子宫肌层细胞膜电位和[Ca2+]的调控。
