Voltage-Gated Proton Channel H V 1 in Microglia

Abstract

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 H_V1 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 H_V1 in the brain is poorly understood. Recent studies showed that H_V1 is selectively expressed in microglia but not neurons in the brain. At the cellular level, microglial H_V1 regulates intracellular pH and aids in NADPH oxidase-dependent generation of reactive oxygen species. In a mouse model of middle cerebral artery occlusion, microglial H_V1 contributes to neuronal cell death and ischemic brain damage. This review discusses the discovery, properties, regulation, and pathophysiology of microglial H_V1 proton channel in the brain.