Microglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer’s Disease

Figure 1

KCa3.1 regulates microglial activation by modulating Ca²⁺ influx. AβO initiates an increase of intracellular Ca²⁺ either directly by forming a Ca²⁺-permeable membrane pore (AβO-Ca²⁺ pore) [11, 12] or indirectly through interaction with a receptor (tentatively termed AβO-R). Intracellular Ca²⁺ activates KCa3.1 to induce K⁺ efflux. The resulting hyperpolarisation provides the driving force for Ca²⁺ entry through store-operated inward-rectifier calcium channels like CRAC, thus sustaining the Ca²⁺ signal necessary for selective Ca²⁺ activated pathways. One example illustrated here is iNOS activation and nitric oxide (NO) production to cause microglia-mediated neurotoxicity.