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Rho-kinase-mediated suppression of K_DR current in cerebral arteries requires an intact actin cytoskeleton

Departments of ¹Physiology and Biophysics and ²Biochemistry and Molecular Biology, University of Calgary, Alberta, Canada

Submitted 17 November 2008 ; accepted in final form 10 February 2009

This study examined the role of the actin cytoskeleton in Rho-kinase-mediated suppression of the delayed-rectifier K⁺ (K_DR) current in cerebral arteries. Myocytes from rat cerebral arteries were enzymatically isolated, and whole cell K_DR currents were monitored using conventional patch-clamp electrophysiology. At +40 mV, the K_DR current averaged 19.8 ± 1.6 pA/pF (mean ± SE) and was potently inhibited by UTP (3 x 10^–5 M). This suppression was observed to depend on Rho signaling and was abolished by the Rho-kinase inhibitors H-1152 (3 x 10^–7 M) and Y-27632 (3 x 10^–5 M). Rho-kinase was also found to concomitantly facilitate actin polymerization in response to UTP. We therefore examined whether actin dynamics played a role in the ability of Rho-kinase to suppress K_DR current and found that actin disruption using either cytochalasin D (1 x 10^–5 M) or latrunculin A (1 x 10^–8 M) prevented current modulation. Consistent with our electrophysiological observations, both Rho-kinase inhibition and actin disruption significantly attenuated UTP-induced depolarization and constriction of cerebral arteries. We propose that UTP initiates Rho-kinase-mediated remodeling of the actin cytoskeleton and consequently suppresses the K_DR current, thereby facilitating the depolarization and constriction of cerebral arteries.

pyrimidine nucleotides; Rho signaling; potassium channels; vascular smooth muscle; delayed-rectifier potassium current

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