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

被引:18
作者
Fomina, Alla F. [1 ]
Nguyen, Hai M. [2 ]
Wulff, Heike [2 ]
机构
[1] Univ Calif Davis, Dept Physiol & Membrane Biol, Davis, CA 95616 USA
[2] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA
关键词
Microglia activation; Kv1; 3; store-operated calcium influx; voltage-gated potassium channel; depolarization; neuroinflammation;
D O I
10.1080/19336950.2020.1853943
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In the last 5 years inhibitors of the potassium channel K(V)1.3 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(V)1.3 blockers on pro-inflammatory microglia functions was not known until our group recently demonstrated that K(V)1.3 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(V)1.3 in microglial signaling and show that, similarly to their role in T cells, K(V)1.3 channels also regulated store-operated calcium influx in microglia.
引用
收藏
页码:67 / 78
页数:12
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