Gating and conductance properties of BK channels are modulated by the S9-S10 tail domain of the alpha subunit. A study of mSlo1 and mSlo3 wild-type and chimeric channels.
Gating and conductance properties of BK channels are modulated by the S9-S10 tail domain of the alpha subunit. A study of mSlo1 and mSlo3 wild-type and chimeric channels.
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DOI：
10.1085/jgp.118.6.711
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发表时间：
2001-12
期刊：
影响因子：
--
通讯作者：
Magleby KL
中科院分区：
文献类型：
--
作者：
Moss BL;Magleby KL
大电导Ca2+活化K+ (BK)通道的cooh末端S9-S10尾部结构域是Ca2+敏感性的主要决定因素（Schreiber， M., a . Wei, a . Yuan， J. Gaut， M. Saito, and L. Salkoff. 1999）。《神经科学》2:16 - 421)。为了研究尾结构域是否也调节BK通道的Ca2+非依赖性，我们研究了BK通道mSlo1和Slo家族的另一个成员mSlo3之间的功能差异（Schreiber， M.， A. Yuan, and L. Salkoff. 1998）。生物。化学273:3509 - 3516)。与mSlo1通道相比，mSlo3通道Ca2+敏感性较低，其平均打开时间、爆发持续时间、爆发间隔和单通道电导分别仅为mSlo1通道的32,22,41和37%。为了研究哪些通道属性来自于尾域，我们将mSlo1的核心与mSlo1的尾域或mSlo3的尾域通道共表达，并研究了单通道电流。将mSlo1尾部替换为mSlo3尾部，结果如下：在Ca2+缺失的情况下，打开概率增加；通过允许Ca2+部分激活和降低Ca2+激活的Hill系数，大大降低了Ca2+敏感性；降低电压依赖性~ 28%；平均开启时间缩短2 - 3倍；减少平均爆发持续时间三到九倍；降低单通道电导~ 14%；使阻滞的K d降低TEAi ~ 30%；在门控过程中，没有改变3到4个打开状态和5到7个关闭状态的最小数量；并且没有改变相邻间隔持续时间之间依赖关系的主要特征。这些观察结果支持BK通道的模块化结构，其中尾域调节电压依赖性核心域的门控动力学和电导特性，除了决定大多数高亲和力Ca2+灵敏度外。
The COOH-terminal S9–S10 tail domain of large conductance Ca2+-activated K+ (BK) channels is a major determinant of Ca2+ sensitivity (Schreiber, M., A. Wei, A. Yuan, J. Gaut, M. Saito, and L. Salkoff. 1999. Nat. Neurosci. 2:416–421). To investigate whether the tail domain also modulates Ca2+-independent properties of BK channels, we explored the functional differences between the BK channel mSlo1 and another member of the Slo family, mSlo3 (Schreiber, M., A. Yuan, and L. Salkoff. 1998. J. Biol. Chem. 273:3509–3516). Compared with mSlo1 channels, mSlo3 channels showed little Ca2+ sensitivity, and the mean open time, burst duration, gaps between bursts, and single-channel conductance of mSlo3 channels were only 32, 22, 41, and 37% of that for mSlo1 channels, respectively. To examine which channel properties arise from the tail domain, we coexpressed the core of mSlo1 with either the tail domain of mSlo1 or the tail domain of mSlo3 channels, and studied the single-channel currents. Replacing the mSlo1 tail with the mSlo3 tail resulted in the following: increased open probability in the absence of Ca2+; reduced the Ca2+ sensitivity greatly by allowing only partial activation by Ca2+ and by reducing the Hill coefficient for Ca2+ activation; decreased the voltage dependence ∼28%; decreased the mean open time two- to threefold; decreased the mean burst duration three- to ninefold; decreased the single-channel conductance ∼14%; decreased the K d for block by TEAi ∼30%; did not change the minimal numbers of three to four open and five to seven closed states entered during gating; and did not change the major features of the dependency between adjacent interval durations. These observations support a modular construction of the BK channel in which the tail domain modulates the gating kinetics and conductance properties of the voltage-dependent core domain, in addition to determining most of the high affinity Ca2+ sensitivity.
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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
DOI：
10.1085/jgp.59.4.388
发表时间：
1972-04
期刊：
The Journal of general physiology
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56.9
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Cui, JM;Aldrich, RW
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Aldrich, RW
DOI：
10.1098/rspb.1997.0104
发表时间：
1997-05-22
影响因子：
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