Modulation of BK channel voltage gating by different auxiliary β subunits
Modulation of BK channel voltage gating by different auxiliary β subunits
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DOI：
10.1073/pnas.1216953109
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发表时间：
2012-11-13
影响因子：
11.1
通讯作者：
Latorre, Ramon
中科院分区：
文献类型：
--
作者：
Contreras, Gustavo F.;Neely, Alan;Latorre, Ramon
钙和电压激活的钾通道（BK）受多种信号的调节。流行的观点是，不同的BK门控机制收敛，以确定通道开放，这些门控机制是变构耦合。在大多数情况下，BK的成孔α亚基与四种替代β亚基之一相关，这些β亚基似乎靶向特定的门控机制以调节通道活性。特别是，β 1稳定BK电压传感器的活性配置，对BK Ca2+灵敏度有很大影响。为了确定β亚基调节BK电压传感器的程度，我们测量了由成孔BK α亚基单独和与爪蟾卵母细胞中表达的不同β亚基（β 1、β 2IR、β 3b和β 4）诱导的门控电流。我们发现β 1、β 2和β 4使BK电压传感器稳定在活性构象中。β 3对电压传感器平衡没有影响。此外，β 4降低了每个电压传感器的表观电荷数。与α β 4通道中的电压传感器相关的电荷减少解释了它们的大部分生物物理特性。对于单独由α亚基组成的通道，门控电荷随着脉冲持续时间缓慢增加，如预期的那样，如果该电荷的显著部分随着与K+电流激活的时间过程相当的时间过程而发展。在β 1、β 2和β 4的存在下，这种缓慢的成分在离子电流激活之前发展，并且比离子电流激活快得多，这表明BK通道开放分两步进行。
Calcium- and voltage-activated potassium channels (BK) are regulated by a multiplicity of signals. The prevailing view is that different BK gating mechanisms converge to determine channel opening and that these gating mechanisms are allosterically coupled. In most instances the pore forming alpha subunit of BK is associated with one of four alternative beta subunits that appear to target specific gating mechanisms to regulate the channel activity. In particular, beta 1 stabilizes the active configuration of the BK voltage sensor having a large effect on BK Ca2+ sensitivity. To determine the extent to which beta subunits regulate the BK voltage sensor, we measured gating currents induced by the pore-forming BK alpha subunit alone and with the different beta subunits expressed in Xenopus oocytes (beta 1, beta 2IR, beta 3b, and beta 4). We found that beta 1, beta 2, and beta 4 stabilize the BK voltage sensor in the active conformation. beta 3 has no effect on voltage sensor equilibrium. In addition, beta 4 decreases the apparent number of charges per voltage sensor. The decrease in the charge associated with the voltage sensor in alpha beta 4 channels explains most of their biophysical properties. For channels composed of the alpha subunit alone, gating charge increases slowly with pulse duration as expected if a significant fraction of this charge develops with a time course comparable to that of K+ current activation. In the presence of beta 1, beta 2, and beta 4 this slow component develops in advance of and much more rapidly than ion current activation, suggesting that BK channel opening proceeds in two steps.