Modulation of endothelial SK3 channel activity by Ca2+-dependent caveolar trafficking
Modulation of endothelial SK3 channel activity by Ca2+-dependent caveolar trafficking
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DOI：
10.1152/ajpcell.00058.2012
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发表时间：
2012-08-01
影响因子：
5.5
通讯作者：
Maylie, James
中科院分区：
文献类型：
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作者：
Lin, Mike T.;Adelman, John P.;Maylie, James
Lin MT，Adelman JP，Maylie J.通过Ca 2+依赖性小窝运输调节内皮SK 3通道活性。美国生理学杂志细胞生理学303：C318-C327，2012年。首次发表于2012年5月23日; doi：10.1152/ajpcell.00058.2012。小电导和中电导Ca 2+激活的K+通道（SK 3/Kcnn 3和IK 1/Kcnn 4）在血管内皮中表达。它们的活性通过调节产生内皮源性血管活性剂所需的细胞内浓度（[Ca 2 +]（i）），在调节血管张力方面发挥重要作用。内皮IK 1或SK 3通道的激活使内皮细胞膜电位超极化，增加Ca 2+内流，并导致血管活性因子的释放，从而影响血压。为了研究IK 1和SK 3通道的不同作用，我们使用电生理记录来研究急性分离的小鼠主动脉内皮细胞中IK 1和SK 3通道的运输。结果表明，SK 3通道在质膜和细胞内细胞器之间进行Ca 2+依赖性循环;破坏Ca 2+依赖性内皮细胞小窝循环可消除SK 3通道运输。此外，递质诱导的SK 3通道活性和表面表达的变化调节内皮细胞膜电位。相比之下，IK 1通道不经历快速运输，并且当胞吞作用或胞吞作用被阻断时，它们的活性保持不变。因此，SK 3表面表达的调节可能在以Ca 2+依赖的方式调节内皮细胞膜电位中起重要作用。
Lin MT, Adelman JP, Maylie J. Modulation of endothelial SK3 channel activity by Ca2+-dependent caveolar trafficking. Am J Physiol Cell Physiol 303: C318-C327, 2012. First published May 23, 2012; doi:10.1152/ajpcell.00058.2012.-Small- and intermediate-conductance Ca2+-activated K+ channels (SK3/Kcnn3 and IK1/Kcnn4) are expressed in vascular endothelium. Their activities play important roles in regulating vascular tone through their modulation of intracellular concentration([Ca2+](i)) required for the production of endothelium-derived vasoactive agents. Activation of endothelial IK1 or SK3 channels hyperpolarizes endothelial cell membrane potential, increases Ca2+ influx, and leads to the release of vasoactive factors, thereby impacting blood pressure. To examine the distinct roles of IK1 and SK3 channels, we used electro-physiological recordings to investigate IK1 and SK3 channel trafficking in acutely dissociated endothelial cells from mouse aorta. The results show that SK3 channels undergo Ca2+-dependent cycling between the plasma membrane and intracellular organelles; disrupting Ca2+-dependent endothelial caveolae cycling abolishes SK3 channel trafficking. Moreover, transmitter-induced changes in SK3 channel activity and surface expression modulate endothelial membrane potential. In contrast, IK1 channels do not undergo rapid trafficking and their activity remains unchanged when either exo- or endocytosis is block. Thus modulation of SK3 surface expression may play an important role in regulating endothelial membrane potential in a Ca2+-dependent manner.