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Effects of IKs channel inhibitors in insulin-secreting INS-1 cells

  • Endocrinology
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Abstract

Potassium channels regulate insulin secretion. The closure of KATP 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 β-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 μM. The other sulfonamide analogue HMR1556 inhibited 48% of the outward current with an IC50 of 7 μM. The chromanol 293B had no effect on tolbutamide-sensitive KATP 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.

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Acknowledgements

We would like to thank Carmen Ilgner and Ines Tegtmeier for skilled technical help. The study was supported by the DFG grant UL 140/4-1, the Köln Fortune Program No. 137/1998/Faculty of Medicine, University of Cologne, a Tübingen fortune grant No. 1346-0-0 and a grant of the German Diabetes Society. S.U. was a recipient of a Heisenberg fellowship.

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  1. Jiping Su

    Present address: Department of Otolaryngology, First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China

Authors and Affiliations

  1. Institute of Neurophysiology, University of Köln, Robert Koch Strasse 39, 50931, Cologne, Germany

    Susanne Ullrich, Jiping Su & Martin Rösler

  2. Institute of Physiology, University of Tübingen, Gmelinstrasse 5, 72076, Tübingen, Germany

    Susanne Ullrich, Felicia Ranta & Florian Lang

  3. Department of Applied Physiology, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany

    Oliver H. Wittekindt

  4. Laboratoires Louis Jeantet, Centre Medical Universitaire, 1 rue Michel Servet, CH-1211, Geneva 4, Switzerland

    Frederic Ris

  5. Sanofi-Aventis Pharma Deutschland GmbH, 65926, Frankfurt, Germany

    Uwe Gerlach

  6. Institute of Physiology, University of Regensburg, Universitätsstrasse 31, 93053, Regensburg, Germany

    Dirk Heitzmann & Richard Warth

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  1. Susanne Ullrich
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Correspondence to Susanne Ullrich.

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Ullrich, S., Su, J., Ranta, F. et al. Effects of IKs channel inhibitors in insulin-secreting INS-1 cells. Pflugers Arch - Eur J Physiol 451, 428–436 (2005). https://doi.org/10.1007/s00424-005-1479-2

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