Regulation of BK channels by auxiliary γ subunits.
Regulation of BK channels by auxiliary γ subunits.
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DOI：
10.3389/fphys.2014.00401
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发表时间：
2014
影响因子：
4
通讯作者：
Yan J
中科院分区：
文献类型：
--
作者：
Zhang J;Yan J
大电导、钙和电压激活的钾（BK）通道在钾通道中具有最大的单通道电导，并且可以通过膜去极化和细胞内钙浓度的增加来激活。 BK 通道由成孔、电压和钙感应 α 亚基组成，可以单独使用，也可以与调节亚基结合使用。 BK通道广泛表达于各种组织和细胞中，包括兴奋性和非兴奋性细胞，并表现出不同的生物物理和药理学特征。这种多样性可以部分地通过翻译后修饰和 α 亚基的选择性剪接（由单个基因 KCNMA1 编码）以及组织特异性 β 亚基调节来解释。最近，发现一种富含亮氨酸重复序列的膜蛋白 LRRC26 与 BK 通道相互作用，并在 BK 通道激活的电压依赖性中引起前所未有的大负移（〜-140 mV）。即使在非兴奋性细胞中接近生理钙浓度和膜电压的情况下，LRRC26 也允许 BK 通道打开。随后，三个 LRRC26 相关蛋白 LRRC52、LRRC55 和 LRRC38 被鉴定为 BK 通道调节剂。这些 LRRC 蛋白在结构和功能上与 BK 通道 β 亚基不同，被指定为 γ 亚基。 γ亚基的发现为BK通道调节增加了一个新的维度，并提高了我们对各种组织和细胞类型中BK通道生理功能的理解。与 BK 通道 β 亚基不同，我们对 γ 亚基的了解在现阶段还非常有限。本文回顾了目前已知的 γ 亚基的结构、调节机制、生理相关性和潜在的治疗意义。
The large-conductance, calcium- and voltage-activated potassium (BK) channel has the largest single-channel conductance among potassium channels and can be activated by both membrane depolarization and increases in intracellular calcium concentration. BK channels consist of pore-forming, voltage- and calcium-sensing α subunits, either alone or in association with regulatory subunits. BK channels are widely expressed in various tissues and cells including both excitable and non-excitable cells and display diverse biophysical and pharmacological characteristics. This diversity can be explained in part by posttranslational modifications and alternative splicing of the α subunit, which is encoded by a single gene, KCNMA1, as well as by tissue-specific β subunit modulation. Recently, a leucine-rich repeat-containing membrane protein, LRRC26, was found to interact with BK channels and cause an unprecedented large negative shift (~-140 mV) in the voltage dependence of the BK channel activation. LRRC26 allows BK channels to open even at near-physiological calcium concentration and membrane voltage in non-excitable cells. Three LRRC26-related proteins, LRRC52, LRRC55, and LRRC38, were subsequently identified as BK channel modulators. These LRRC proteins are structurally and functionally distinct from the BK channel β subunits and were designated as γ subunits. The discovery of the γ subunits adds a new dimension to BK channel regulation and improves our understanding of the physiological functions of BK channels in various tissues and cell types. Unlike BK channel β subunits, which have been intensively investigated both mechanistically and physiologically, our understanding of the γ subunits is very limited at this stage. This article reviews the structure, modulatory mechanisms, physiological relevance, and potential therapeutic implications of γ subunits as they are currently understood.
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影响因子：
56.9
作者：
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通讯作者：
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影响因子：
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DOI：
10.1073/pnas.1216953109
发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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