Department of Experimental Medicine, University of Perugia, p.le Gambuli 1, 06123, Perugia, Italy.
Department of Chemistry, Biology and Biotechnology, University of Perugia, via Pascoli 8, 06123, Perugia, Italy.
Curr Neuropharmacol. 2018;16(5):608-617. doi: 10.2174/1570159X15666170830122402.
The KCa3.1 channel is the intermediate-conductance member of the Ca2+- activated K channel superfamily. It is widely expressed in excitable and non-excitable cells, where it plays a major role in a number of cell functions. This paper aims at illustrating the main structural, biophysical and modulatory properties of the KCa3.1 channel, and providing an account of experimental data on its role in volume regulation and Ca2+ signals.
Research and online content related to the structure, structure/function relationship, and physiological role of the KCa3.1 channel are reviewed.
Expressed in excitable and non-excitable cells, the KCa3.1 channel is voltage independent, its opening being exclusively gated by the binding of intracellular Ca2+ to calmodulin, a Ca2+- binding protein constitutively associated with the C-terminus of each KCa3.1 channel α subunit. The KCa3.1 channel activates upon high affinity Ca2+ binding, and in highly coordinated fashion giving steep Hill functions and relatively low EC50 values (100-350 nM). This high Ca2+ sensitivity is physiologically modulated by closely associated kinases and phosphatases. The KCa3.1 channel is normally activated by global Ca2+ signals as resulting from Ca2+ released from intracellular stores, or by the refilling influx through store operated Ca2+ channels, but cases of strict functional coupling with Ca2+-selective channels are also found. KCa3.1 channels are highly expressed in many types of cells, where they play major roles in cell migration and death. The control of these complex cellular processes is achieved by KCa3.1 channel regulation of the driving force for Ca2+ entry from the extracellular medium, and by mediating the K+ efflux required for cell volume control.
Much work remains to be done to fully understand the structure/function relationship of the KCa3.1 channels. Hopefully, this effort will provide the basis for a beneficial modulation of channel activity under pathological conditions.
KCa3.1 通道是钙激活钾通道超家族的中等电导成员。它广泛表达于可兴奋和非兴奋细胞，在许多细胞功能中发挥重要作用。本文旨在阐明 KCa3.1 通道的主要结构、生物物理和调节特性，并提供其在体积调节和钙信号中的作用的实验数据。
综述了与 KCa3.1 通道的结构、结构/功能关系和生理作用相关的研究和在线内容。
在可兴奋和非兴奋细胞中表达的 KCa3.1 通道是电压独立的，其开放仅由细胞内 Ca2+与钙调蛋白结合来门控，钙调蛋白是一种与每个 KCa3.1 通道α亚基的 C 端组成性结合的 Ca2+结合蛋白。KCa3.1 通道在高亲和力 Ca2+结合时激活，并以高度协调的方式产生陡峭的 Hill 函数和相对较低的 EC50 值（100-350 nM）。这种高 Ca2+敏感性受紧密相关的激酶和磷酸酶的生理调节。KCa3.1 通道通常由细胞内储存释放的 Ca2+引起的全局 Ca2+信号或通过储存操作 Ca2+通道的再填充流入激活，但也存在与 Ca2+选择性通道严格功能偶联的情况。KCa3.1 通道在许多类型的细胞中高度表达，在这些细胞中，它们在细胞迁移和死亡中发挥主要作用。这些复杂的细胞过程的控制是通过 KCa3.1 通道调节 Ca2+从细胞外介质进入的驱动力以及介导细胞体积调节所需的 K+外流来实现的。
要充分了解 KCa3.1 通道的结构/功能关系，还有很多工作要做。希望这项工作将为在病理条件下有益地调节通道活性提供基础。
