Kv1.3 inhibition attenuates neuroinflammation through disruption of microglial calcium signaling.

In the last 5 years inhibitors of the potassium channel K1.3 have been shown to reduce neuroinflammation in rodent models of ischemic stroke, Alzheimer's disease, Parkinson's disease and traumatic brain injury. At the systemic level these beneficial actions are mediated by a reduction in microglia activation and a suppression of pro-inflammatory cytokine and nitric oxide production. However, the molecular mechanisms for the suppressive action of K1.3 blockers on pro-inflammatory microglia functions was not known until our group recently demonstrated that K1.3 channels not only regulate membrane potential, as would be expected of a voltage-gated potassium channel, but also play a crucial role in enabling microglia to resist depolarizations produced by the danger signal ATP thus regulating calcium influx through P2X4 receptors. We here review the role of K1.3 in microglial signaling and show that, similarly to their role in T cells, K1.3 channels also regulated store-operated calcium influx in microglia.