K+ channel modulation in arterial smooth muscle

Abstract

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 (K V) are encoded by the Kv gene family, Ca 2+‐activated K+ channels (BK Ca) are encoded by the slo gene, inward rectifiers (K IR) by Kir2.0, and ATP‐sensitive K+ channels (K ATP) 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 β 1–β 4, slo α and β, 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 K ATP channels. These include adenosine, calcitonin gene‐related peptide, and β‐adrenoceptor agonists. β‐adrenoceptors can also activate BK Ca and K V channels. Several vasoconstrictors that activate protein kinase C inhibit K ATP channels, and inhibition of BK Ca and K V channels through PKC has also been described. Activators of cGMP‐dependent protein kinase, in particular NO, activate BK Ca channels, and possibly K ATP channels. Hypoxia leads to activation of K ATP channels, and activation of BK Ca channels has also been reported. Hypoxic pulmonary vasoconstriction involves inhibition of K V channels. Vasodilation to increased external K+ involves K IR 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.