BK+ channels contribute to the cellular activation of microglia: A big channel in small glia

Ca²⁺-activated K⁺ (KCa) channels are classified into three major subtypes based on conductance size: BK, IK and SK. Increases in intracellular Ca2+ induce channel opening, resulting in K+ efflux that maintains a driving force for subsequent Ca2+ influx. Therefore, KCa channels in excitable cells such as neurons work as breaks to prevent excessive excitation. In contrast, K_Ca channels in non-excitable cells such as T-cells and microglia work as accelerators to induce cellular activation, proliferation and migration. There is increasing evidence that hyperactive microglia play pathological roles in neurodegenerative diseases, neuropsychiatric disorders and chronic pain. Recently, optically pure S-ketaminehas been shown to preferentially suppress nerve injuryinduceddevelopment of tactile allodynia and hyperactivation of spinal microglia through the blockade of BK channels in microglia. We herein describe the current understanding of the biophysiological properties, proposed functions and modulatory molecules of BK channels in microglia.