Hv1 proton channel opening is preceded by a voltage-independent transition.
Hv1 proton channel opening is preceded by a voltage-independent transition.
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DOI：
10.1016/j.bpj.2014.08.017
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发表时间：
2014-10
影响因子：
3.4
通讯作者：
C. Villalba-Galea
中科院分区：
文献类型：
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作者：
C. Villalba-Galea
电压门控质子通道Hv 1的电压敏感结构域（VSD）介导H+选择性电导，该电导由膜电位（V）和跨膜pH梯度（ΔpH）协调控制。通过ΔpH（V-ΔpH偶联）对Hv 1通道开放的变构控制表现为活化中每ΔpH单位约40 mV的特征性位移。为了进一步理解Hv 1中V-ΔpH偶联的机制，分析了H+电流激活和失活的动力学，作为膜电位和膜细胞内侧pH（pHI）的函数。在这项研究中，据我们所知，它是第一次显示，Hv 1的开放之前的电压无关的过渡。已经提出了一个类似的过程来构成涉及四聚体电压门控通道中的电压敏感域和孔域之间的偶联的步骤。然而，对于Hv 1，VSD的功能作为电压传感器和传导途径，这表明电压无关的过渡是固有的电压感测域。因此，本文提出，激活Hv 1的潜在机制涉及一个类似于VSD松弛的过程，这是一个先前描述的电压门控通道和电压控制酶的过程。最后，失活似乎发生作为一个严格的电压依赖性的过程，这意味着动力学事件，导致开放的质子电导是不同的那些参与关闭。因此，从这项工作中提出，Hv 1活动显示滞后。
The voltage sensing domain (VSD) of the voltage-gated proton channel Hv1 mediates a H+-selective conductance that is coordinately controlled by the membrane potential (V) and the transmembrane pH gradient (ΔpH). Allosteric control of Hv1 channel opening by ΔpH (V-ΔpH coupling) is manifested by a characteristic shift of approximately 40 mV per ΔpH unit in the activation. To further understand the mechanism forV-ΔpH coupling in Hv1, H+current kinetics of activation and deactivation in excised membrane patches were analyzed as a function of the membrane potential and the pH in the intracellular side of the membrane (pHI). In this study, it is shown for the first time to our knowledge that the opening of Hv1 is preceded by a voltage-independent transition. A similar process has been proposed to constitute the step involving coupling between the voltage-sensing and pore domains in tetrameric voltage-gated channels. However, for Hv1, the VSD functions as both the voltage sensor and the conduction pathway, suggesting that the voltage independent transition is intrinsic to the voltage-sensing domain. Therefore, this article proposes that the underlying mechanism for the activation of Hv1 involves a process similar to VSD relaxation, a process previously described for voltage-gated channels and voltage-controlled enzymes. Finally, deactivation seemingly occurs as a strictly voltage dependent process, implying that the kinetic event leading to opening of the proton conductance are different than those involved in the closing. Thus, from this work it is proposed that Hv1 activity displays hysteresis.