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

ABSTRACT

In the last 5 years inhibitors of the potassium channel K_V1.3 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 K_V1.3 blockers on pro-inflammatory microglia functions was not known until our group recently demonstrated that K_V1.3 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 K_V1.3 in microglial signaling and show that, similarly to their role in T cells, K_V1.3 channels also regulated store-operated calcium influx in microglia.

KEYWORDS:

• Microglia activation
• Kv1.3
• store-operated calcium influx
• voltage-gated potassium channel
• depolarization
• neuroinflammation

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by a National Institute of Neurological Disease and Stroke award NS100294 (to H.W.) and a UC Davis School of Medicine Research Partnership Grant (to AFF).