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(Circulation Research. 2000;87:83.)
© 2000 American Heart Association, Inc.

Editorial

Knockout Blow for Channel Identity Crisis

Vasodilation to Potassium Is Mediated via Kir2.1

Christopher G. Sobey, Frank M. Faraci

From the Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia; Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa.

Correspondence to Frank M. Faraci, PhD, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242-1081. E-mail frank-faraci@uiowa.edu

Key Words: potassium channels • genetics • mice • cerebral arteries

	Introduction

 
The normal concentration of potassium ion (K⁺) in extracellular fluid is 3 to 5 mmol/L.¹ In contrast to the depolarization and contraction of vascular muscle that are commonly produced by high concentrations of K⁺, small to moderate increases in the concentration of extracellular K⁺ produce membrane hyperpolarization and relaxation in a variety of blood vessels in vitro.^{2 3 4 5 6 7 8 9} This vasodilator response is particularly prominent in cerebral arteries.^{2 3 4 5} Because K⁺ is released during normal neuronal and muscle activity, this mechanism may play a role in the coupling of cellular metabolism and local blood flow.^{10 11 12}

Several mechanisms have been proposed to contribute to K⁺-induced hyperpolarization of vascular muscle and vasodilatation. The two most studied have been (1) increased activation of Na⁺/K⁺-ATPase and (2) increased activity of inwardly rectifying K⁺ channels (Kir).^{2 3 4 8} These studies have relied almost exclusively on the use of pharmacological inhibition with ouabain and extracellular barium ion (Ba²⁺), respectively. Although a ouabain-sensitive vascular response may be present for very modest increases in extracellular K⁺ (<5 mmol/L), the major sustained component elicited by higher concentrations of K⁺ (7 to 20 mmol/L) is Ba²⁺-sensitive.^{2 3 4 5 8} Because of these findings, recent interest has focused on Kir channels as the key signaling pathway that produces vasodilatation through physiological elevations in extracellular K⁺.

K⁺ channels are thought to play a major role in regulation of vascular tone by producing hyperpolarization of vascular muscle in response to diverse stimuli including receptor-mediated agonists, second messengers, and Ca²⁺ sparks.^{13 14 15} Hyperpolarization of vascular . . . [Full Text of this Article]

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