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

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Citations

Apr 26, 2008·Pflügers Archiv : European journal of physiology·Won Sun ParkYung E Earm
Apr 5, 2005·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·William F Jackson
Jan 24, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Francesco VetriDale A Pelligrino
Sep 26, 2012·PPAR Research·Neerupma SilswalJon Andresen
May 7, 2004·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Iris SeitzUte Lindauer
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Dec 6, 2012·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xiao Yan Huang, Chang Xun Chen
Aug 28, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Dan YeHon-Chi Lee
Oct 16, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Hiroyuki KinoshitaYoshio Hatano
Feb 7, 2004·Stroke; a Journal of Cerebral Circulation·Sophocles Chrissobolis, Christopher G Sobey
Jul 25, 2006·The Journal of Pharmacology and Experimental Therapeutics·Wei ZhouHon-Chi Lee
Feb 3, 2006·The Journal of Pharmacology and Experimental Therapeutics·Klaudia BudzynChristopher G Sobey
Aug 28, 2004·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Benedek ErdösDavid W Busija

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