Effects of the hypoglycaemic drugs repaglinide and glibenclamide on ATP-sensitive potassium-channels and cytosolic calcium levels in Β TC3 cells and rat pancreatic beta cells
✍ Scribed by J. Gromada; S. Dissing; H. Kofod; J. FrØkjÆr-Jensen
- Publisher
- Springer
- Year
- 1995
- Tongue
- English
- Weight
- 807 KB
- Volume
- 38
- Category
- Article
- ISSN
- 0012-186X
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✦ Synopsis
The present study demonstrates the action of the hypoglycaemic drugs repaglinide and glibenclamide in cultured newborn rat islet cells and mouse flTC3 cells. In cell-attached membrane patches of newborn rat islet cells repaglinide (10 nmol/ 1) and glibenclamide (20 nmol/1) decrease the open probability of single ATP-sensitive K + -channels to approximately 10 % of the activity prior to addition of the drugs in short-term experiments (< 5 min). The influence of repaglinide and glibenclamide on the ATP-sensitive K + current was studied using the whole-cell patch clamp configuration. A half-maximal steady-state inhibition of the ATP-sensitive K + currents is observed at 89 pmol/1 repaglinide and at 47 pmol/1 glibenclamide in whole-cell experiments of longer duration (30 min). Applying digital Ca 2 + imaging on single flTC3 cells we found that repaglinide and glibenclamide induced a concentration-dependent increase in intracellular free Ca 2+ concentration ([Ca 2 +]i) with a half-maximal effect at 0.5 nmol/1 for both drugs in long-term experiments (30 min). The rise in [Ca 2+ ]i results from Ca 2+ entry through voltage-dependent L-type Ca 2+ -channels since it is inhibited by verapamil (10 ~mol/1). The effect of repaglinide and glibenclamide is partly reversible (= 80 %).