Allosteric linkage between voltage and Ca2+-dependent activation of BK-tgype mslo1 K+ channels
Allosteric linkage between voltage and Ca2+-dependent activation of BK-tgype mslo1 K+ channels
复制标题
DOI：
10.1021/bi001509
复制
发表时间：
2000-12-19
期刊：
影响因子：
2.9
通讯作者：
Aldrich, RW
中科院分区：
文献类型：
--
作者：
Cui, JM;Aldrich, RW
BK型Ca2+激活的K+通道的激活依赖于电压和Ca2+。我们研究了mslol BK通道中假定的电压传感器S4或S4- s5连接区域的三个点突变，以探索电压和Ca2+在激活通道中的关系。这些突变降低了打开概率-电压（P-o - V）关系的陡度，增加了P-o - V关系在电压轴上随钙浓度增加而发生的位移。令人惊讶的是，尽管突变对通道门控电压依赖性的其他方面有不同的影响，但这两种效应对所有三种突变都是相互相关的。这种互反关系强烈表明，电压和钙结合对通道激活的自由能贡献只是相加的。我们得出结论，Ca2+结合位点和电压传感器不直接相互作用。相反，它们都通过变构机制，通过影响封闭构象和开放构象之间的构象变化来影响基质通道的打开。突变改变了通道的电压依赖性，对其Ca2+亲和力影响不大。
The activation of BK type Ca2+-activated K+ channels depends on both voltage and Ca2+ We studied three point mutations in the putative voltage sensor S4 or S4-S5 linker regions in the mslol BK channels to explore the relationship between voltage and Ca2+ in activating the channel. These mutations reduced the steepness of the open probability - voltage (P-o - V) relation and increased the shift of the P-o - V relations on the voltage axis in response to increases in the calcium concentration. It is striking that these two effects were reciprocally related for all three mutations, despite different effects of the mutations on other aspects of the voltage dependence of channel gating. This reciprocal relationship suggests strongly that the free energy contributions to channel activation provided by voltage and by calcium binding are simply additive. We conclude that the Ca2+ binding sites and the voltage sensors do not directly interact. Rather they both affect the mslol channel opening through an allosteric mechanism, by influencing the conformational change between the closed and open conformations. The mutations changed the channel's voltage dependence with little effect on its Ca2+ affinity.