Microglial Voltage-Gated Proton Channel Hv1 in Neurological Disorders

The voltage-gated proton channel, Hv1, is a newly discovered ion channel that is highly expressed in the immune system. Upon activation, the channel rapidly removes protons from depolarized cytoplasm, aiding in acid extrusion from the cell. In the central nervous system (CNS), Hv1 is selectively expressed in microglia but not neurons or astrocytes. Microglial Hv1 modulates intracellular pH homeostasis. In addition, Hv1 promotes NADPH oxidase-dependent production of reactive oxygen species (ROS) via charge compensation and proton balance. Emerging evidence sheds light on the role of microglial Hv1 in a repertoire of neuropathological conditions such as ischemic stroke, spinal cord injury, multiple sclerosis, and glioblastoma. This chapter will provide a comprehensive overview on the discovery, properties, regulation, and physiology of microglial Hv1 proton channel. Further, the chapter discusses the molecular mechanisms and functional significance of microglial Hv1 in the context of the various neurological disorders and highlights the opportunities in targeting the proton channel Hv1 for therapeutic gain.