Yu Shen1,2 · Yuncheng Luo1,2 · Ping Liao2 · Yunxia Zuo1,2 · Ruotian Jiang1,2
1 Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610000, China
2 Laboratory of Anesthesia and Critical Care Medicine, National‑Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610000, China
Hv1 is the only voltage-gated proton-selective channel in mammalian cells. It contains a conserved voltage-sensor domain, shared by a large class of voltage-gated ion channels, but lacks a pore domain. Its primary role is to extrude protons from the cytoplasm upon pH reduction and membrane depolarization. The best-known function of Hv1 is the regulation of cytosolic pH and the nicotinamide adenine dinucleotide phosphate oxidase-dependent production of reactive oxygen species. Accumulating evidence indicates that Hv1 is expressed in nervous systems, in addition to immune cells and others. Here, we summarize the molecular properties, distribution, and physiological functions of Hv1 in the peripheral and central nervous systems. We describe the recently discovered functions of Hv1 in various neurological diseases, including brain or spinal cord injury, ischemic stroke, demyelinating diseases, and pain. We also summarize the current advances in the discovery and application of Hv1-targeted small molecules in neurological diseases. Finally, we discuss the current limitations of our understanding of Hv1 and suggest future research directions.
Voltage-gated ion channel; Hv1; Proton; ROS; Neuroinflammation; Neurological diseases; Pain