Jun 8, 2002

Inhibitory effects of protein kinase C on inwardly rectifying K+- and ATP-sensitive K+ channel-mediated responses of the basilar artery

Stroke; a Journal of Cerebral Circulation
Sophocles Chrissobolis, Christopher G Sobey

Abstract

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. 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. 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 th...Continue Reading

  • References24
  • Citations18

Citations

Mentioned in this Paper

Potassium Channel Blockers
Naphthalenes
Neogluconin
Resting Potentials
Potassium
Inward rectifier potassium channel
Barium
UCN 1028 C
Vascular Endothelium-Dependent Relaxation
Vasoactive Antagonists

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