Title: Physiological and Pathophysiological Roles of ATP-Sensitive K+ Channels in Vascular Smooth Muscle
Volume: 4
Issue: 2
Author(s): Noriyoshi Teramoto and William C. Cole
Affiliation:
Keywords:
ATP-sensitive K+ channels, hypoxia, K+ channels, vascular smooth muscle, sulphonylureas
Abstract: The presence of K+ channels that are sensitive to intracellular ATP concentration ([ATP]i) was first described for ventricular myocytes and referred to as ATP-sensitive K+ channels (i.e. KATP channels). Subsequently, K+ channels with similar physiological characteristics were demonstrated to be expressed by many other cells types including pancreatic β-cells, skeletal muscle fibres, central neurons, cortical neurons and smooth muscle. It is now apparent that these channels play important roles in coupling cellular electrical activity to the metabolic status of cells. Molecular biological approaches have been employed to clone the protein subunits which form KATP channels. These studies indicate that the channels are composed of at least two protein subunits: (i) inwardly-rectifying K+ channel (Kir) subunits of the Kir6.x family that form the ion conducting pore and (ii) modulatory, sulphonylurea receptor (SUR) subunits, a member of the ATP-binding cassette (ABC) protein super-family, which accounts for several pharmacological properties of the channels. Determination of the molecular basis of native vascular KATP channels and smooth muscle-specific KATP subunit composition is essential for a comprehensive understanding of the physiological and pathophysiological roles of the channels in controlling smooth muscle contractility, sulphonylurea drug- and KATP channel opener-sensitivity and control of channel gating (opening and closing) by kinase-mediated phosphorylation. The purpose of this review is to briefly to overview the current knowledge available concerning KATP channels, with the primary focus being the molecular basis of native KATP channels and their possible linkage to pathophysiological function in vascular smooth muscle.
