Ullrich, Susanne and Su, J.P. and Ranta, F. and Wittekindt, O.H. and Ris, F. and Rosler, M. and Gerlach, U. and Heitzmann, D. and Warth, Richard and Lang, F. (2005) Effects of I-Ks channel inhibitors in insulin-secreting INS-1 cells. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 451 (3). pp. 428-436. ISSN 0031-6768,
Full text not available from this repository. (Request a copy)Abstract
Potassium channels regulate insulin secretion. The closure of K-ATP channels leads to membrane depolarisation, which triggers Ca2+ influx and stimulates insulin secretion. The subsequent activation of K+ channels terminates secretion. We examined whether KCNQ1 channels are expressed in pancreatic beta-cells and analysed their functional role. Using RT/PCR cellular mRNA of KCNQ1 but not of KCNE1 channels was detected in INS-1 cells. Effects of two sulfonamide analogues, 293B and HMR1556, inhibitors of KCNQ1 channels, were examined on voltage-activated outwardly rectifying K+ currents using the patch-clamp method. It was found that 293B inhibited 60% of whole-cell outward currents induced by voltage pulses from -70 to +50 mV with a concentration for half-maximal inhibition (IC50) of 37 mu M. The other sulfonamide analogue HMR1556 inhibited 48% of the outward current with an IC50 of 7 mu M. The chromanol 293B had no effect on tolbutamide-sensitive K-ATP channels. Action potentials induced by current injections were broadened and after-repolarisation was attenuated by 293B. Insulin secretion in the presence but not in the absence of tolbutamide was significantly increased by 293B. These results suggest that 293B- and HMR1556-sensitive channels, probably in concert with other voltage-activated K+ channels, influence action potential duration and frequency and thus insulin secretion.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PANCREATIC BETA-CELLS; DEPENDENT K+ CHANNELS; POTASSIUM CHANNEL; CHROMANOL 293B; EXTERNAL TETRAETHYLAMMONIUM; INDUCED HYPERPOLARIZATION; ISLET CELLS; LINE INS-1; SK PROTEIN; GLUCOSE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Apr 2021 11:37 |
| Last Modified: | 20 Apr 2021 11:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35389 |
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