CALCIUM-ACTIVATED K+ CHANNELS AS MODULATORS OF HUMAN MYOMETRIAL CONTRACTILE ACTIVITY
CALCIUM-ACTIVATED K+ CHANNELS AS MODULATORS OF HUMAN MYOMETRIAL CONTRACTILE ACTIVITY
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DOI：
10.1152/ajpcell.1993.265.4.c976
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发表时间：
1993-10-01
影响因子：
--
通讯作者：
TORO, L
中科院分区：
文献类型：
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作者：
ANWER, K;OBERTI, C;TORO, L
研究了子宫平滑肌和子宫肌细胞中 Ca2+ 激活钾 (K(Ca)) 通道在膜电位、细胞内游离钙 ([Ca2+]i) 和收缩调节中的作用。在永生化人子宫肌层细胞系中，催产素增加[Ca2+]i 和[H-3]磷酸肌醇的形成。松弛素减弱催产素诱导的 [Ca2+]i 增加。在细胞附着的斑块中，膜去极化激活了大电导 K(Ca) 通道 (179 +/- 4 pS)。伊比利亚毒素 (IbTX)，“maxi”K(Ca) 通道的有效阻断剂（A. Galvez、G. Gimenez-Gallego、J. P. Reuben、L. Roy-Contanciin、P. Feigenbaum、G. J. Kaczorowski 和 M. L. Garcia. J. Biol. Chem. 265：11083-11090， 1990）制作了长期封闭的赛事（大约 6 分钟）在这些频道中。与这种阻断一致，IbTX 使细胞去极化 9.8 +/- 2.8 mV，并导致 [Ca2+] 剂量依赖性增加，半最大有效浓度为 0.79 nM。 IbTX 还引起人类子宫肌层的阶段性收缩，并增加雌激素引发的大鼠子宫肌层自发收缩的频率和力量。此外，子宫肌层收缩力也受到 1 mM 四乙铵的影响，该浓度当应用于细胞外侧时会阻断子宫平滑肌 K(Ca) 通道 (G. J. Perez, L. Toro, S. D. Erulkar, and E. Stefani. Am. J. Obstet. Gynecol. 168:652-660, 1993)。这些结果强烈表明大电导K(Ca)通道可能积极参与人类子宫肌细胞膜电位和[Ca2+]i的控制。
The role of Ca2+-activated potassium (K(Ca)) 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 [H-3]inositol phosphate formation. Relaxin attenuated the oxytocin-induced increase in [Ca2+]i. In cell-attached patches, membrane depolarization activated a large-conductance K(Ca) channel (179 +/- 4 pS). Iberiotoxin (IbTX), a potent blocker of ''maxi'' K(Ca) 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+], 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 K(Ca) 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 K(Ca) channels may actively participate in the control of human myometrial cell membrane potential and [Ca2+]i.