Zhang Xue, Zeng Xuhui, Xia Xiao-Ming, Lingle Christopher J
Department of Anesthesiology and Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Gen Physiol. 2006 Sep;128(3):301-15. doi: 10.1085/jgp.200609551.
Here we have examined the voltage and pH dependence of unitary Slo3 channels and used analysis of current variance to define Slo3 unitary current properties over a broader range of voltages. Despite complexity in Slo3 channel openings that precludes simple definition of the unitary conductance, average current through single Slo3 channels varies linearly with voltage at positive activation potentials. Furthermore, the average Slo3 unitary current at a given activation potential does not change with pH. Consistent with macroscopic conductance estimates, the apparent open probability of Slo3 channel exhibits a pH-dependent maximum, with limiting values around 0.3 at the most elevated pH and voltage. Estimates of Slo3 conductance at negative potentials support a weaker intrinsic voltage dependence of gating than is observed for Slo1. For the pH-regulated Slo3 K(+) channel, the dependence of macroscopic conductance on pH suggests that the pH-sensitive mechanism regulates gating in an allosteric manner qualitatively similar to regulation of Slo1 by Ca(2+). Together, the results support the view that the regulation of macroscopic Slo3 currents by pH reflects regulation of gating equilibria, and not a direct effect of pH on ion permeation. Specifically, both voltage and pH regulate a closed-open conformational change in a largely independent fashion.
在此,我们研究了单个Slo3通道的电压和pH依赖性,并通过电流方差分析在更广泛的电压范围内定义了Slo3单通道电流特性。尽管Slo3通道开放存在复杂性,使得无法简单定义单通道电导,但在正激活电位下,通过单个Slo3通道的平均电流随电压呈线性变化。此外,在给定激活电位下,平均Slo3单通道电流不随pH变化。与宏观电导估计一致,Slo3通道的表观开放概率呈现出pH依赖性最大值,在最高pH和电压下极限值约为0.3。在负电位下对Slo3电导的估计表明,其门控的内在电压依赖性比Slo1弱。对于pH调节的Slo3钾通道,宏观电导对pH的依赖性表明,pH敏感机制以与Ca(2+)对Slo1调节在性质上相似的变构方式调节门控。总之,这些结果支持这样一种观点,即pH对宏观Slo3电流的调节反映了门控平衡的调节,而不是pH对离子通透的直接影响。具体而言,电压和pH在很大程度上以独立的方式调节关闭-开放构象变化。