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 microM) reversibly decreased 86Rb efflux from the islets, whereas adrenaline was ineffective at concentrations up to 100 microM. 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 microM) caused a marked acceleration of 86Rb efflux from the islets, which was attenuated by 100 microM 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 microM, clonidine reversibly inhibited the ATP-sensitive K+ current in a dose-dependent manner. 5. Voltage-sensitive K+ currents were unaffected by 20 microM but decreased slightly by 100 microM clonidine. 6. Calcium currents, measured by the whole cell or perforated patch technique, were unaffected by clonidine at concentrations up to 100 microM. 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.