Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (Caesar), Bonn, Germany.
Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps-University Marburg, Marburg, Germany.
Sci Rep. 2020 Dec 4;10(1):21293. doi: 10.1038/s41598-020-77986-z.
The voltage-gated proton channel Hv1 is expressed in a variety of cells, including macrophages, sperm, and lung epithelial cells. Hv1 is gated by both the membrane potential and the difference between the intra- and extracellular pH (ΔpH). The coupling of voltage- and ∆pH-sensing is such that Hv1 opens only when the electrochemical proton gradient is outwardly directed. However, the molecular mechanism of this coupling is not known. Here, we investigate the coupling between voltage- and ΔpH-sensing of Ciona intestinalis proton channel (ciHv1) using patch-clamp fluorometry (PCF) and proton uncaging. We show that changes in ΔpH can induce conformational changes of the S4 voltage sensor. Our results are consistent with the idea that S4 can detect both voltage and ΔpH.
电压门控质子通道 Hv1 表达于多种细胞中,包括巨噬细胞、精子和肺上皮细胞。Hv1 由膜电位和细胞内外 pH 值差(ΔpH)共同门控。这种电压和 pH 值感应的偶联使得只有在外向质子电化学梯度时 Hv1 才会打开。然而,这种偶联的分子机制尚不清楚。在这里,我们使用膜片钳荧光法(PCF)和质子去笼技术研究了海鞘质子通道(ciHv1)的电压和 pH 值感应的偶联。我们表明,ΔpH 的变化可以诱导 S4 电压传感器构象的变化。我们的结果与 S4 可以同时检测电压和 ΔpH 的观点一致。