Basolateral K+ channels in airway epithelia. I. Regulation by Ca2+ and block by charybdotoxin.
Basolateral K+ channels in airway epithelia. I. Regulation by Ca2+ and block by charybdotoxin.
复制标题
气道上皮的基底外侧 K 通道。
DOI：
10.1152/ajplung.1990.258.6.l334
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Welsh,MJ
中科院分区：
文献类型：
--
作者：
McCann,JD;Matsuda,J;Garcia,M;Kaczorowski,G;Welsh,MJ
在气道上皮细胞中，环磷酸腺苷（cAMP）通过激活顶膜Cl-通道和基底膜K+通道刺激Cl-分泌。Cl-通道受cAMP依赖性磷酸化调节，而K+通道受胞质Ca 2+浓度[Ca 2 +]c调节。我们最近观察到cAMP增加[Ca ~（2+）]c，提示cAMP可能通过增加[Ca ~（2+）]c间接调节K ~+通道。为了研究K+通道的调节，我们测量了86 Rb流出，膜补丁中的单个K+通道，和[Ca 2 +]c与荧光指示剂Fura-2。异丙肾上腺素和Ca ~（2+）离子载体A23187瞬时增加[Ca ~（2+）]c，瞬时刺激86 Rb流出。细胞内Ca ~（2+）库的释放刺激了~（86）Rb的外排。Ba ~（2+）或Charybdotoxin可阻断~（86）Rb的外排，而四乙基铵则不能阻断~（86）Rb的外排。Charybdotoxin阻止所有的86 Rb流出，刺激A23187或毛喉素。Charybdotoxin也阻断膜斑的低电导内向整流钾通道（KCLIC）。这些结果表明，KCLIC通道负责气道上皮细胞中K+通透性的Ca 2（+）依赖性增加。它们还表明cAMP诱导的细胞内Ca 2+释放足以激活K+通道。
In airway epithelia, adenosine 3',5'-cyclic monophosphate (cAMP) stimulates Cl- secretion by activating apical membrane Cl- channels and basolateral membrane K+ channels. Cl- channels are regulated by cAMP-dependent phosphorylation, whereas K+ channels are regulated by the cytosolic Ca2+ concentration, [Ca2+]c. Our recent observation that cAMP increases [Ca2+]c suggested that cAMP might indirectly regulate K+ channels by increasing [Ca2+]c. To study regulation of K+ channels we measured 86Rb efflux, single K+ channels in membrane patches, and [Ca2+]c with the fluorescent indicator fura-2. Isoproterenol and Ca2+ ionophore, A23187, transiently increased [Ca2+]c and transiently stimulated 86Rb efflux. Stimulation of 86Rb efflux resulted from release of intracellular Ca2+ stores. 86Rb efflux was blocked by Ba2+ or charybdotoxin, but not by tetraethylammonium. Charybdotoxin prevented all of the 86Rb efflux that was stimulated by A23187 or by forskolin. Charybdotoxin also blocked the low-conductance inwardly rectifying K+ channel (KCLIC) in membrane patches. These results indicate that the KCLIC channel is responsible for the Ca2(+)-dependent increase in K+ permeability in airway epithelial cells. They also indicate that cAMP-induced release of intracellular Ca2+ is sufficient to activate K+ channels.