Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits.
Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits.
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DOI：
10.3389/fphys.2014.00383
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发表时间：
2014
影响因子：
4
通讯作者：
Latorre R
中科院分区：
文献类型：
--
作者：
Torres YP;Granados ST;Latorre R
大电导电压和Ca ~（2+）激活的K ~+通道（BK）由一个基因（Slo 1，KCM）编码，由去极化电位和细胞内Ca ~（2+）浓度升高激活，是K ~+通道超家族中唯一的一个。BK通道是一种四聚体，其特征是一个成孔α亚基，含有7个跨膜片段（而不是电压依赖性K+通道中的6个）和一个由两个K+传导结构域（RCK结构域）调节剂组成的大C末端，其中存在Ca 2+结合位点。BK通道可以与辅助β亚基相关，尽管已经描述了不同的BK调节机制，但由于其生理重要性，最近对β亚基在BK通道门控调节中可能发挥的作用产生了更大的兴趣。目前已经鉴定出四种β亚基（即，β1、β2、β3和β4），尽管事实上它们都具有相同的拓扑结构，但已经表明每个β亚基都具有特定的组织分布，并且它们以不同的方式改变通道动力学以及它们的药理学性质和α亚基的表观Ca 2+敏感性。此外，不同的研究表明，天然的、内源性的和合成的化合物可以通过β亚基调节BK通道。考虑到这些通道在不同病理状态下的重要性，如高血压和神经系统疾病，本文综述了这些化合物通过调节β亚基来调节BK通道的生物物理特性的机制，以及它们在上述疾病中的潜在治疗用途。
Coded by a single gene (Slo1, KCM) and activated by depolarizing potentials and by a rise in intracellular Ca2+ concentration, the large conductance voltage- and Ca2+-activated K+ channel (BK) is unique among the superfamily of K+ channels. BK channels are tetramers characterized by a pore-forming α subunit containing seven transmembrane segments (instead of the six found in voltage-dependent K+ channels) and a large C terminus composed of two regulators of K+ conductance domains (RCK domains), where the Ca2+-binding sites reside. BK channels can be associated with accessory β subunits and, although different BK modulatory mechanisms have been described, greater interest has recently been placed on the role that the β subunits may play in the modulation of BK channel gating due to its physiological importance. Four β subunits have currently been identified (i.e., β1, β2, β3, and β4) and despite the fact that they all share the same topology, it has been shown that every β subunit has a specific tissue distribution and that they modify channel kinetics as well as their pharmacological properties and the apparent Ca2+ sensitivity of the α subunit in different ways. Additionally, different studies have shown that natural, endogenous, and synthetic compounds can modulate BK channels through β subunits. Considering the importance of these channels in different pathological conditions, such as hypertension and neurological disorders, this review focuses on the mechanisms by which these compounds modulate the biophysical properties of BK channels through the regulation of β subunits, as well as their potential therapeutic uses for diseases such as those mentioned above.
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影响因子：
3.6
作者：
Bukiya, Anna N.;McMillan, Jacob E.;Dopico, Alex M.
通讯作者：
Dopico, Alex M.
影响因子：
3.8
作者：
Anderson, C S;MacKinnon, R;Smith, C;Miller, C
通讯作者：
Miller, C
DOI：
10.1073/pnas.1317363111
发表时间：
2014-06-24
影响因子：
11.1
作者：
Bukiya, Anna N.;Kuntamallappanavar, Guruprasad;Dopico, Alex M.
通讯作者：
Dopico, Alex M.
影响因子：
--
作者：
De Wet, Heidi;Allen, Marcus;Callaghan, Richard
通讯作者：
Callaghan, Richard
影响因子：
64.8
作者：
BOLOTINA, VM;NAJIBI, S;COHEN, RA
通讯作者：
COHEN, RA