CLONIDINE INHIBITS ATP-SENSITIVE K+ CHANNELS IN MOUSE PANCREATIC BETA-CELLS

1 The effects of clonidine and adrenaline on adenosine 5'-triphosphate (ATP)-sensitive K+ channels were studied in pancreatic beta-cells from normal mice. 2 When perifused with a medium containing 1 mM glucose, many of the ATP-sensitive K+ channels in the beta-cell membrane are open. Under these conditions, clonidine (5-100-mu-M) reversibly decreased Rb-86 efflux from the islets, whereas adrenaline was ineffective at concentrations up to 100-mu-M. 3 In 6 mM glucose, most of the ATP-sensitive K+ channels in the beta-cell membrane are closed. Opening these channels by diazoxide (100-mu-M) caused a marked acceleration of Rb-86 efflux from the islets, which was attenuated by 100-mu-M clonidine. 4 ATP-sensitive K+ currents were measured in single beta-cells by the whole cell mode of the patch-clamp technique. At concentrations above 4-mu-M, clonidine reversibly inhibited the ATP-sensitive K+ current in a dose-dependent manner. 5 Voltage-sensitive K+ currents were unaffected by 20-mu-M but decreased slightly by 100-mu-M clonidine. 6 Calcium currents, measured by the whole cell or perforated patch technique, were unaffected by clonidine at concentrations up to 100-mu-M. 7 It is concluded that high concentrations of the alpha-2-adrenoceptor agonist clonidine, but not of adrenaline, can inhibit ATP-sensitive K+ channels in pancreatic beta-cells. Other ionic channels are only slightly affected or unaffected.