Structure and Function of ATP-Sensitive K+ Channels

Abstract

ATP-sensitive K⁺channels_(KATPchannels) were first described by NOMA (1983) in cardiac muscle using the patch clamp technique. KATP channels are characterized by channel inhibition with an increase in intracellular ATP concentration and stimulation with an increase in intracellular MgADP concentration (DUNNE and PETERSEN 1986; KAKEI et al. 1986; MISLER et al. 1986). KATP channels are also found in many other tissues including pancreatic ß-cells (COOK and HALES 1984; ASHCROFT and RORSMAN 1989), skeletal muscles (DAVIES et al. 1991), neurons, kidney, and various smooth muscles (KURIYAMA et al. 1995; QUAYLE et al. 1997), and also in mitochondria (INOUE et al. 1991; PAUCEK et al. 1992). In several tissues, however, the presence of KATP_ATP channels has not been shown directly by electrophysiology, but by other physiological and pharmacological methods. For example, the presence of KATP_ATP channels in brain (GRIGG and ANDERSON 1989; POLITI and ROGAWSKI 1991; MURPHY and GREENFIELD 1991; JIANG et al. 1992; TROMBA et al. 1992) and vascular tissues (VON BECKERATH et al. 1991; SILBERBERG and VAN BREEMEN 1992: DART and STANDEN 1995; KATNIK and ADAMS 1995) has been shown by the increase of K⁺ conductance in energy depleting conditions and pharmacological modifications of the response. Similarly, an increase in K⁺ conductance after the addition of KATP_ATP channel openers such as diazoxide or cromakalim (Fig. 1), or a decrease in conductance by the addition of KATP_atp channel blockers, sulfonylureas such as glibenclamide or tolbutamide (Fig. 1) which are widely used in the treatment of non-insulin dependent diabetes mellitus (NIDDM), has also revealed the presence of KATP_atp channels in brain and various smooth muscle cells.