Clonidine inhibits ATP‐sensitive K+channels in mouse pancreatic β‐cells

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Abstract
1 The effects of clonidine and adrenaline on adenosine 5′-triphosphate (ATP)-sensitive K+channels were studied in pancreatic β-cells from normal mice. 2 When perifused with a medium containing 1 mm glucose, many of the ATP-sensitive K+channels in the β-cell membrane are open. Under these conditions, clonidine (5–100 μm) reversibly decreased 86Rb efflux from the islets, whereas adrenaline was ineffective at concentrations up to 100 μm. 3 In 6 mm glucose, most of the ATP-sensitive K+channels in the β-cell membrane are closed. Opening these channels by diazoxide (100 μm) caused a marked acceleration of 86Rb efflux from the islets, which was attenuated by 100 μm clonidine. 4 ATP-sensitive K+currents were measured in single β-cells by the whole cell mode of the patch-clamp technique. At concentrations above 4 μm, clonidine reversibly inhibited the ATP-sensitive K+current in a dose-dependent manner. 5 Voltage-sensitive K+currents were unaffected by 20 μm but decreased slightly by 100 μm clonidine. 6 Calcium currents, measured by the whole cell or perforated patch technique, were unaffected by clonidine at concentrations up to 100 μm. 7 It is concluded that high concentrations of the α2-adrenoceptor agonist clonidine, but not of adrenaline, can inhibit ATP-sensitive K+channels in pancreatic β-cells. Other ionic channels are only slightly affected or unaffected.