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


  • 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 micromol/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 micromol/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 micromol/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.

publication date

  • June 2002

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