Recent studies have indicated that arachidonic acid is primarily metabolized by cytochromeP-450 (CYP) enzymes in the brain, lung, kidney, and peripheral vasculature to 20-hydroxyeicosatetraenoic ac...

P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function

Exercise is the most important physiological stimulus for increased myocardial oxygen demand. The requirement of exercising muscle for increased blood flow necessitates an increase in cardiac outpu...

Regulation of Coronary Blood Flow During Exercise

In this review, we present the basic properties, physiological functions, regulation, and pathological alterations of four major classes of K+ channels that have been detected in vascular smooth muscle cells. Voltage-dependent K+ (Kv) channels open upon depolarization of the plasma membrane in vascular smooth muscle cells. The subsequent efflux of K+ through the channels induces repolarization to the resting membrane potential. Changes in the intracellular Ca2+ concentration and membrane depolarization stimulate large-conductance Ca2+-activated K+ (BKCa) channels, which are thought to play an important role in maintaining the membrane potential. ATP-sensitive K+ (K(ATP)) channels underscore the functional bond between cellular metabolism and membrane excitability. The blockade of KATP channel function results in vasoconstriction and depolarization in various types of vascular smooth muscle. Inward rectifier K+ (Kir) channels, which are expressed in smooth muscle of the small-diameter arteries, contribute to the resting membrane potential and basal tone. Kir channel activation has been shown to raise the extracellular K+ concentration to 10-15 mM, resulting in vasodilation. Each of K+ channels listed above is responsive to a number of vasoconstrictors and vasodilators, which act through protein kinase C (PKC) and protein kinase A (PKA), respectively. Impaired Kv, KATP, and Kir channel functions has been linked to a number of pathological conditions, which may lead to vasoconstriction.

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Physiological roles of K+ channels in vascular smooth muscle cells.

Physiological roles of K^+ channels in vascular smooth muscle cells(Hirosi Kuriyama Award 2007 Memorial Review)

The regulation of trabecular meshwork and ciliary muscle contractility.

Potassium channels play an essential role in the membrane potential of arterial smooth muscle, and also in regulating contractile tone. Four types of K+ channel have been described in vascular smooth muscle: Voltage-activated K+ channels (Kv) are encoded by the Kv gene family, Ca(2+)-activated K+ channels (BKCa) are encoded by the slo gene, inward rectifiers (KIR) by Kir2.0, and ATP-sensitive K+ channels (KATP) by Kir6.0 and sulphonylurea receptor genes. In smooth muscle, the channel subunit genes reported to be expressed are: Kv1.0, Kv1.2, Kv1.4-1.6, Kv2.1, Kv9.3, Kv beta 1-beta 4, slo alpha and beta, Kir2.1, Kir6.2, and SUR1 and SUR2. Arterial K+ channels are modulated by physiological vasodilators, which increase K+ channel activity, and vasoconstrictors, which decrease it. Several vasodilators acting at receptors linked to cAMP-dependent protein kinase activate KATP channels. These include adenosine, calcitonin gene-related peptide, and beta-adrenoceptor agonists. beta-adrenoceptors can also activate BKCa and Kv channels. Several vasoconstrictors that activate protein kinase C inhibit KATP channels, and inhibition of BKCa and Kv channels through PKC has also been described. Activators of cGMP-dependent protein kinase, in particular NO, activate BKCa channels, and possibly KATP channels. Hypoxia leads to activation of KATP channels, and activation of BKCa channels has also been reported. Hypoxic pulmonary vasoconstriction involves inhibition of Kv channels. Vasodilation to increased external K+ involves KIR channels. Endothelium-derived hyperpolarizing factor activates K+ channels that are not yet clearly defined. Such K+ channel modulations, through their effects on membrane potential and contractile tone, make important contributions to the regulation of blood flow.

J M Quayle

Papers

K+ channel modulation in arterial smooth muscle