Rho‐kinase‐mediated suppression of KDR in cerebral arteries requires an intact actin cytoskeleton

Abstract

This study examined the role of the actin cytoskeleton in Rho‐kinase‐mediated suppression of the delayed rectifier K+ (KDR) current in cerebral arteries. Myocytes from rat cerebral arteries were enzymatically isolated and whole cell KDR currents monitored using conventional patch clamp electrophysiology. At +40 mV, the KDR current averaged 19.8 ± 1.6 pA/pF (mean ± SE) and was potently inhibited by uridine triphosphate (UTP; 50 μM). Consistent with past observations, KDR suppression was blocked by the Rho‐kinase inhibitor Y‐27632 (30 μM). Likewise, disruption of the actin cytoskeleton using cytochalasin D (10 μM) or latrunculin A (10 nM) abolished the ability of UTP to suppress KDR. Interestingly, these agents inhibited the current when used at higher concentrations, further suggesting a mechanistic link between the actin cytoskeleton and channels underlying the KDR current. These preliminary findings suggest that an intact cytoskeletal framework is a requisite for Rho‐kinase‐mediated suppression of KDR current and the subsequent depolarization and constriction of cerebral arteries. Supported by CIHR and HSFC.