Activation of Ca(2+) -activated Cl(-) channel ANO1 by localized Ca(2+) signals.
Activation of Ca(2+) -activated Cl(-) channel ANO1 by localized Ca(2+) signals.
复制标题
通过局部 Ca(2 ) 信号激活 Ca(2 ) 激活的 Cl(-) 通道 ANO1。
DOI：
10.1113/jphysiol.2014.275107
复制
发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Gamper N
中科院分区：
文献类型：
--
作者：
Jin X;Shah S;Du X;Zhang H;Gamper N
钙激活的氯离子通道(CaCCs)调节多种生理过程，包括上皮运输、平滑肌收缩和感觉加工。Anoctamin-1(ANO1，TMEM16A)是许多细胞类型中主要的CACC亚单位，但我们对ANO1的激活和调节机制的了解才刚刚开始。ANO1对Ca~(2+)的敏感性很低，在负膜电位下，该通道需要几个微摩尔的细胞内钙离子才能激活。然而，细胞内的整体钙水平很少达到这样的水平，因此，一定存在将细胞内钙瞬变集中到ANO1通道的机制。最近的发现确实表明，ANO1通道经常与细胞内钙信号的来源共定位。有趣的是，在许多类型的细胞中，ANO1似乎特别紧密地耦合到细胞内钙库中的钙释放部位。这种优先偶联可能代表了天然组织中ANO1激活的一般机制。
Ca2+‐activated chloride channels (CaCCs) regulate numerous physiological processes including epithelial transport, smooth muscle contraction and sensory processing. Anoctamin‐1 (ANO1, TMEM16A) is a principal CaCC subunit in many cell types, yet our understanding of the mechanisms of ANO1 activation and regulation are only beginning to emerge. Ca2+ sensitivity of ANO1 is rather low and at negative membrane potentials the channel requires several micromoles of intracellular Ca2+ for activation. However, global Ca2+ levels in cells rarely reach such levels and, therefore, there must be mechanisms that focus intracellular Ca2+ transients towards the ANO1 channels. Recent findings indeed indicate that ANO1 channels often co‐localize with sources of intracellular Ca2+ signals. Interestingly, it appears that in many cell types ANO1 is particularly tightly coupled to the Ca2+ release sites of the intracellular Ca2+ stores. Such preferential coupling may represent a general mechanism of ANO1 activation in native tissues.