Kv7 potassium channels as therapeutic targets in cerebral vasospasm

Abstract

Cerebral vasospasm is a devastating medical consequence of aneurysmal subarachnoid hemorrhage (aSAH), which is associated with a high level of morbidity and mortality and for which current therapies are inadequate. Ion channels in the smooth muscle cells of the cerebral vasculature have been considered as important molecular targets for anti-vasospastic therapies, but, other than the calcium channel blocker nimodipine, no therapies directed toward these targets have been demonstrated to improve patient outcomes. Recent research has revealed that a family of previously identifi ed neuronal voltage-activated potassium channels, Kv7 (KCNQ) channels, is expressed in arterial smooth muscle cells, including cerebral arterial myocytes. This fi nding, along with the availability of clinically used drugs that were developed to target the neuronal Kv7 channels, provides an opportunity to develop novel therapeutic strategies to relieve or prevent cerebral vasospasm. Recent studies using both in vitro and in vivo approaches provide evidence to support the utility of Kv7 channel activators as anti-vasospastic agents, while revealing a number of additional potentially benefi cial effects that could attenuate other neurological or infl ammatory co-morbidities associated with aSAH.