Physiological roles of ATP‐sensitive K⁺ channels in smooth muscle

Abstract

Potassium channels that are inhibited by intracellular ATP (ATP i ) were first identified in ventricular myocytes, and are referred to as ATP-sensitive K + channels (i.e. K ATP channels). Subsequently, K + channels with similar characteristics have been demonstrated in many other tissues (pancreatic β-cells, skeletal muscle, central neurones, smooth muscle). Approximately one decade ago, K ATP channels were cloned and were found to be composed of at least two subunits: an inwardly rectifying K + channel six family (Kir6.x) that forms the ion conducting pore and a modulatory sulphonylurea receptor (SUR) that accounts for several pharmacological properties. Various types of native K ATP channels have been identified in a number of visceral and vascular smooth muscles in single-channel recordings. However, little attention has been paid to the molecular properties of the subunits in K ATP channels and it is important to determine the relative expression of K ATP channel components which give rise to native K ATP channels in smooth muscle. The aim of this review is to briefly discuss the current knowledge available for K ATP channels with the main interest in the molecular basis of native K ATP channels, and to discuss their possible linkage with physiological functions in smooth muscle.

Inhibitory effect of tramadol on vasorelaxation mediated by ATP-sensitive K+ channels in rat aorta

“…The K ATP channel is composed of at least two subunits: an inwardly rectifying K + channel six family that forms an ion conducting pore, and a modulatory sulfonylurea receptor that accounts for the pharmacologic properties of several drugs such as levcromakalim and glibenclamide. 14 In agreement with previous studies, 2,6,7 glibenclamide almost abolished the vasorelaxation mediated by levcromakalim in the rat aorta. A pretreatment with glibenclamide completely abolished the tramadol-induced attenuation of the vasorelaxant response induced by levcromakalim.…”

“…A pretreatment with glibenclamide completely abolished the tramadol-induced attenuation of the vasorelaxant response induced by levcromakalim. These results suggest that tramadol attenuates the vasorelaxation mediated by levcromakalim through its effect on some of the components of the sulfonylurea receptor 14 of the K ATP channels. S(+) tramadol and the metabolite (+)-O-desmethyltramadol (M1) are agonists of the µ-opioid receptors.…”

Oxidative Stress Inhibits Vascular KATP Channels by S-Glutathionylation

“…H 2 O 2 Inhibited Kir6.1/SUR2B Channel Activity in the Presence of GSH-The Kir6.1/SUR2B channel is the major isoform of vascular K ATP channels (6,19,20). Thus, we studied its modulation by expressing the Kir6.1/SUR2B channel in HEK293 cells.…”

“…Activity of the channels is inhibited by vasoconstrictors (5), resulting in depolarization of the SMCs and vasoconstriction. Such a common vascular regulator is thus targeted by a variety of cellular events in physiological and pathological conditions (1,6).…”

Ontogeny of sulfonylurea-binding regulatory subunits of KATP channels in the pregnant rat myometrium

“…Both subunits (SURs and Kir 6.x ) are necessary for the channel function. Kir 6.x comprises the K C channel component of the K ATP , whereas the SURs are responsible for the ATP sensitivity, pharmacological properties, and trafficking of this channel , Gross et al 1999, Bryan et al 2004, Teramoto 2006, Ko et al 2008. The molecular structure of the K ATP channels is different due to the heterologous expression of Kir 6.x and the SUR subunits.…”