Effects of I(Ks) channel inhibitors in insulin-secreting INS-1 cells

Pflugers Arch. 2005 Dec;451(3):428-36. doi: 10.1007/s00424-005-1479-2. Epub 2005 Aug 30.


Potassium channels regulate insulin secretion. The closure of K(ATP) channels leads to membrane depolarisation, which triggers Ca(2+) 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 (IC(50)) of 37 microM. The other sulfonamide analogue HMR1556 inhibited 48% of the outward current with an IC(50) of 7 microM. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine
  • Animals
  • Cell Line, Tumor
  • Chromans / pharmacology*
  • Gene Expression
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / physiology*
  • KCNQ1 Potassium Channel / physiology*
  • Membrane Potentials
  • Rats
  • Sulfonamides / pharmacology*
  • Tetraethylammonium
  • Tolbutamide


  • Chromans
  • HMR 1556
  • Insulin
  • KCNQ1 Potassium Channel
  • Sulfonamides
  • 6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane
  • Tetraethylammonium
  • Tolbutamide
  • 4-Aminopyridine