Biophysical properties of the voltage gated proton channel H(V)1.

Biophysical properties of the voltage gated proton channel H(V)1.
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DOI:
10.1002/wmts.55
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发表时间:
2012-09-01
期刊:
Wiley interdisciplinary reviews. Membrane transport and signaling
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电压门控质子通道(HV1)的生物物理特性是其生理功能的关键要素。电压门控质子通道是一种独特的分子,与所有其他离子通道相比,它对质子具有排他性选择性。在质子通道中,它与其他“经典”离子通道一样具有电压和时间依赖性门控。此外,HV1还是细胞和周围介质中pH值的传感器。其电压依赖性与跨膜的pH梯度严格耦合。这种调节将通道的开放限制在任何给定pH梯度下的特定电压,因此允许HV1在其表达的组织中执行其生理任务。对于HV1,没有已知的阻滞剂。最有效的通道抑制剂是锌(Zn2+),其阻止通道开放。HV1的另一个特性是其门控和电导的强温度依赖性。与单行水填充孔(如短杆菌肽通道)相比,HV1对传导表现出明显的氘效应和温度效应,与其他离子通道不同的传导机制一致。这些属性可以解释最近确定的天冬氨酸在孔的HV1是必不可少的质子选择性。
The biophysical properties of the voltage gated proton channel (HV1) are the key elements of its physiological function. The voltage gated proton channel is a unique molecule that in contrast to all other ion channels is exclusively selective for protons. Alone among proton channels, it has voltage and time dependent gating like other “classical” ion channels. HV1 is furthermore a sensor for the pH in the cell and the surrounding media. Its voltage dependence is strictly coupled to the pH gradient across the membrane. This regulation restricts opening of the channel to specific voltages at any given pH gradient, therefore allowing HV1 to perform its physiological task in the tissue it is expressed in. For HV1 there is no known blocker. The most potent channel inhibitor is zinc (Zn2+) which prevents channel opening. An additional characteristic of HV1 is its strong temperature dependence of both gating and conductance. In contrast to single-file water filled pores like the gramicidin channel, HV1 exhibits pronounced deuterium effects and temperature effects on conduction, consistent with a different conduction mechanism than other ion channels. These properties may be explained by the recent identification of an aspartate in the pore of HV1 that is essential to its proton selectivity.