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Clonidine inhibits ATP-sensitive K+ channels in mouse pancreatic beta-cells
T D Plant1, J C Jonas, J C Henquin
1I. Physiologisches Institut, Universität des Saarlandes, Homburg (Saar), Germany.
Abstract:
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.
Insights
Clonidine, but not adrenaline, inhibits ATP-sensitive potassium channels in pancreatic beta-cells. This effect was observed at high concentrations, impacting cellular function and ion channel activity.
Area of Science:
- Endocrinology
- Molecular Pharmacology
- Cell Physiology
Background:
- Adenosine 5'-triphosphate (ATP)-sensitive K+ channels play a crucial role in regulating insulin secretion from pancreatic beta-cells.
- Understanding the modulatory effects of adrenergic agents on these channels is vital for comprehending beta-cell function and potential therapeutic interventions.
Purpose of the Study:
- To investigate the impact of clonidine and adrenaline on ATP-sensitive K+ channels in mouse pancreatic beta-cells.
- To determine the specific effects on ion channel activity and their dose-dependency.
Main Methods:
- Studied 86Rb efflux from pancreatic islets under varying glucose concentrations.
- Utilized patch-clamp techniques (whole-cell and perforated patch) to measure ATP-sensitive K+ currents, voltage-sensitive K+ currents, and calcium currents in single beta-cells.
- Administered clonidine and adrenaline at various concentrations.
Main Results:
- Clonidine (5-100 microM) reversibly decreased 86Rb efflux in low glucose conditions, while adrenaline was ineffective.
- Clonidine (100 microM) attenuated diazoxide-induced 86Rb efflux in high glucose conditions.
- Clonidine dose-dependently inhibited ATP-sensitive K+ currents at concentrations above 4 microM.
- Voltage-sensitive K+ currents were slightly decreased by 100 microM clonidine, while calcium currents remained unaffected.
Conclusions:
- High concentrations of the alpha 2-adrenoceptor agonist clonidine inhibit ATP-sensitive K+ channels in pancreatic beta-cells.
- Adrenaline does not significantly affect these channels under the studied conditions.
- Other ionic channels in pancreatic beta-cells are minimally affected or unaffected by clonidine at the tested concentrations.