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(Stroke. 2002;33:1692.)
© 2002 American Heart Association, Inc.

Original Contributions

Inhibitory Effects of Protein Kinase C on Inwardly Rectifying K⁺- and ATP-Sensitive K⁺ Channel-Mediated Responses of the Basilar Artery

Sophocles Chrissobolis, BSc(Hons) Christopher G. Sobey, PhD

From the Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.

Correspondence to Christopher G. Sobey, PhD, Department of Pharmacology, University of Melbourne, Parkville, Victoria 3010, Australia. E-mail cgsobey{at}unimelb.edu.au

Background and Purpose— The structurally related, inwardly rectifying K⁺ (K_IR) channel and the ATP-sensitive K⁺ (K_ATP) channel are important modulators of cerebral artery tone. Although protein kinase C (PKC) activators have been shown to inhibit these channels with the use of patch-clamp electrophysiology, effects of PKC on K⁺ channel function in intact cerebral blood vessels are unknown. We therefore tested whether pharmacological alteration of PKC activity affects cerebral vasodilator responses to K_IR and/or K_ATP channel activators in vivo.

Methods— We measured changes in basilar artery diameter using a cranial window preparation in anesthetized rats. In addition, intracellular recordings of smooth muscle membrane potential were made in isolated basilar arteries.

Results— K⁺ (5 to 15 mmol/L) and aprikalim (1 to 10 µmol/L) each elicited reproducible vasodilatation. The PKC activator phorbol-12,13-dibutyrate (PdBu) (50 nmol/L) inhibited responses to K⁺ (by 40% to 55%) and aprikalim (by 40% to 70%), whereas responses to papaverine were unaffected. The PKC inhibitor calphostin C (0.1 µmol/L) augmented responses to K⁺ (by 2- to 3-fold) and aprikalim (2-fold) but not papaverine. In addition, K⁺ (5 mmol/L) and aprikalim (3 µmol/L) each hyperpolarized the basilar artery. PdBu inhibited these responses to aprikalim by 45% but had no effect on K⁺-induced hyperpolarization.

Conclusions— These data suggest that both basal and stimulated PKC activity inhibit K_IR and K_ATP channel–mediated cerebral vasodilatation in vivo. The inhibitory effect on K_ATP channel–mediated vasodilatation occurs at least partly by inhibition of hyperpolarization mediated by K_ATP channels. PKC inhibits K⁺-induced vasodilatation without affecting hyperpolarization, suggesting that the inhibitory effect of PKC on vasodilator responses to K⁺ does not involve altered K_IR channel function.

Key Words: basilar artery • potassium • potassium channels • protein kinases • rats

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