Gating and ionic currents reveal how the BKCa channel's Ca2+ sensitivity is enhanced by its beta1 subunit.
Gating and ionic currents reveal how the BKCa channel's Ca2+ sensitivity is enhanced by its beta1 subunit.
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DOI：
10.1085/jgp.200509346
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发表时间：
2005-10
期刊：
影响因子：
--
通讯作者：
Cox DH
中科院分区：
文献类型：
--
作者：
Bao L;Cox DH
大电导Ca 2+激活的K+通道（BKCa通道）由辅助β亚基的组织特异性表达调节。β1主要在平滑肌中表达，在那里它大大增强BKCa通道的Ca2+敏感性，这是适当调节平滑肌张力所需的作用。在这里，使用门控电流记录，宏观离子电流记录，和单一的离子电流记录在非常低的开放概率，我们已经调查了这种效果的机制。我们的结果可以总结如下。β1亚基对BKCa通道打开的构象变化的平衡常数几乎没有影响，并且它不影响通道的电压传感器上的门控电荷，但它确实在通道打开和关闭时稳定电压传感器激活，使得电压传感器激活在β1存在的情况下在更负的电压下发生。此外，β1在通道关闭时比在通道打开时更稳定有源电压传感器，并且这将电压传感器激活促进打开的因子D减小了24%（16.8→12.8）。β1对电压感知的影响通过在大多数电压下降低Ca2+结合打开通道所必须做的功来增强BKCa通道的Ca2+敏感性。然而，为了充分解释β1在负电压下带来的功效和表观Ca2+亲和力的增加，我们的研究表明β1也降低了闭合通道的真实Ca2+亲和力，将其Ca2+解离常数从1.33.7 μM增加到4.7和7.1 μM之间，这取决于有多少结合位点受到影响。
Large-conductance Ca2+-activated K+ channels (BKCa channels) are regulated by the tissue-specific expression of auxiliary β subunits. β1 is predominately expressed in smooth muscle, where it greatly enhances the BKCa channel's Ca2+ sensitivity, an effect that is required for proper regulation of smooth muscle tone. Here, using gating current recordings, macroscopic ionic current recordings, and unitary ionic current recordings at very low open probabilities, we have investigated the mechanism that underlies this effect. Our results may be summarized as follows. The β1 subunit has little or no effect on the equilibrium constant of the conformational change by which the BKCa channel opens, and it does not affect the gating charge on the channel's voltage sensors, but it does stabilize voltage sensor activation, both when the channel is open and when it is closed, such that voltage sensor activation occurs at more negative voltages with β1 present. Furthermore, β1 stabilizes the active voltage sensor more when the channel is closed than when it is open, and this reduces the factor D by which voltage sensor activation promotes opening by ∼24% (16.8→12.8). The effects of β1 on voltage sensing enhance the BKCa channel's Ca2+ sensitivity by decreasing at most voltages the work that Ca2+ binding must do to open the channel. In addition, however, in order to fully account for the increase in efficacy and apparent Ca2+ affinity brought about by β1 at negative voltages, our studies suggest that β1 also decreases the true Ca2+ affinity of the closed channel, increasing its Ca2+ dissociation constant from ∼3.7 μM to between 4.7 and 7.1 μM, depending on how many binding sites are affected.
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DOI：
10.1085/jgp.109.5.647
发表时间：
1997-05
期刊：
The Journal of general physiology
影响因子：
--
作者：
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通讯作者：
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影响因子：
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通讯作者：
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10.1085/jgp.200409052
发表时间：
2004-05
期刊：
The Journal of general physiology
影响因子：
--
作者：
Bao L;Kaldany C;Holmstrand EC;Cox DH
通讯作者：
Cox DH
DOI：
10.1085/jgp.116.3.411
发表时间：
2000-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Cox DH;Aldrich RW
通讯作者：
Aldrich RW