Voltage-gated proton channel HV1 in microglia

Microglia are brain resident immune cells and their functions are implicated in both the normal and diseased brain. Microglia express a plethora of ion channels, including K+ channels, Na+ channels, TRP channels, Cl- channels, and proton channels. These ion channels play critical roles in microglial proliferation, migration, and production/release of cytokines, chemokines, and neurotoxic or neurotrophic substances. Among microglial ion channels, the voltage-gated proton channel HV1 is a recently cloned ion channel that rapidly removes protons from depolarized cytoplasm and is highly expressed in the immune system. However, the function of microglial HV1 in the brain is poorly understood. Recent studies showed that HV1 is selectively expressed in microglia but not neurons in the brain. At the cellular level, microglial HV1 regulates intracellular pH and aids in NADPH oxidase-dependent generation of reactive oxygen species. In a mouse model of middle cerebral artery occlusion, microglial HV1 contributes to neuronal cell death and ischemic brain damage. This review discusses the discovery, properties, regulation, and pathophysiology of microglial HV1 proton channel in the brain.