Ion Channels and Receptors as Determinants of Microglial Function

Microglia provide immune surveillance of the CNS. They display diverse behaviors, including nondirectional and directed motility of their processes, phagocytosis of targets such as dying neurons or superfluous synapses, and generation of reactive oxygen species (ROS) and cytokines. Many of these functions are mediated by ion channels and cell surface receptors, the expression of which varies with the many morphological and functional states that microglial cells can adopt. Recent progress in understanding microglial function has been facilitated by applying classical cell physiological techniques in situ, such as patch-clamping and live imaging, and cell-specific transcriptomic analyses. Here, we review the contribution of microglial ion channels and receptors to microglial and brain function. Essential microglial functions depend on membrane potential and ion channels. Microglial surveillance is regulated by THIK-1 K+ channels, whereas directed process motility is controlled by purinergic signaling and Cl− channels. Enhanced K+ efflux via THIK-1 and Kv channels is needed for NLRP3 inflammasome assembly. Microglial ion channel and receptor expression in culture often differ from those in situ, which results in different morphological and functional states.