Role of the beta1 subunit in large-conductance Ca(2+)-activated K(+) channel gating energetics. Mechanisms of enhanced Ca(2+) sensitivity.
Role of the beta1 subunit in large-conductance Ca(2+)-activated K(+) channel gating energetics. Mechanisms of enhanced Ca(2+) sensitivity.
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DOI：
10.1085/jgp.116.3.411
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发表时间：
2000-09
期刊：
影响因子：
--
通讯作者：
Aldrich RW
中科院分区：
文献类型：
--
作者：
Cox DH;Aldrich RW
在过去的几年里，人们已经清楚地认识到，大电导Ca2+激活的K+通道（BKCa）活性被调节的一个重要机制是辅助β亚基的组织特异性表达。首先确定的β1主要在平滑肌中表达，并产生显著的影响，在0 mV时将通道对Ca2+的表观亲和力提高10倍，并在9.1 μM Ca2+时移动通道激活- 80 mV的电压范围。通过这项研究，我们解决了这样一个问题：β1改变了BKCa门控的哪些方面，从而带来了这些影响：Ca2+结合，电压传感，还是通道打开的内在能量学？我们采用的方法是在爪蟾卵母细胞中表达β1亚基和BKCa α亚基，然后比较β1在大范围Ca2+浓度和膜电压下的稳态效应与通过变构模型预测的稳态效应，变构模型的参数已经改变，以模拟上述门控方面的变化。我们的分析结果表明，β1的稳态效应可以通过通道必须克服的内在能量的减少和电压敏感性的降低来解释，而通道对Ca2+的亲和力在打开或关闭时几乎没有变化。然而，有趣的是，我们的分析表明Ca2+结合亲和力的微小变化（Kc = 7.4 μM→9.6 μM; Ko = 0.80 μM→0.65 μM）似乎在功能上很重要。我们还发现，在Ca2+基本缺失的情况下，β1会影响mSlo的电导电压关系，将其移动+20 mV，并减少38%的表观门控电荷，我们开发了区分Ca2+结合变化和BKCa通道门控其他方面的方法，这些方法可能是通用的。
Over the past few years, it has become clear that an important mechanism by which large-conductance Ca2+-activated K+ channel (BKCa) activity is regulated is the tissue-specific expression of auxiliary β subunits. The first of these to be identified, β1, is expressed predominately in smooth muscle and causes dramatic effects, increasing the apparent affinity of the channel for Ca2+ 10-fold at 0 mV, and shifting the range of voltages over which the channel activates −80 mV at 9.1 μM Ca2+. With this study, we address the question: which aspects of BKCa gating are altered by β1 to bring about these effects: Ca2+ binding, voltage sensing, or the intrinsic energetics of channel opening? The approach we have taken is to express the β1 subunit together with the BKCa α subunit in Xenopus oocytes, and then to compare β1's steady state effects over a wide range of Ca2+ concentrations and membrane voltages to those predicted by allosteric models whose parameters have been altered to mimic changes in the aspects of gating listed above. The results of our analysis suggest that much of β1's steady state effects can be accounted for by a reduction in the intrinsic energy the channel must overcome to open and a decrease in its voltage sensitivity, with little change in the affinity of the channel for Ca2+ when it is either open or closed. Interestingly, however, the small changes in Ca2+ binding affinity suggested by our analysis (Kc 7.4 μM → 9.6 μM; Ko = 0.80 μM → 0.65 μM) do appear to be functionally important. We also show that β1 affects the mSlo conductance–voltage relation in the essential absence of Ca2+, shifting it +20 mV and reducing its apparent gating charge 38%, and we develop methods for distinguishing between alterations in Ca2+ binding and other aspects of BKCa channel gating that may be of general use.
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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：
Cui J;Cox DH;Aldrich RW
通讯作者：
Aldrich RW
内部BA2+与平滑肌的克隆Ca（2+） - 依赖性K+（HSLO）通道的相互作用。
影响因子：
3.8
作者：
Diaz, F;Wallner, M;Stefani, E;Toro, L;Latorre, R
通讯作者：
Latorre, R
影响因子：
4.8
作者：
Brenner, R;Jegla, TJ;Aldrich, RW
通讯作者：
Aldrich, RW
DOI：
10.1085/jgp.99.6.841
发表时间：
1992-06
期刊：
The Journal of general physiology
影响因子：
--
作者：
Markwardt F;Isenberg G
通讯作者：
Isenberg G
影响因子：
3.5
作者：
Meera, P;Wallner, M;Toro, L
通讯作者：
Toro, L