| 16133261 |
Ullrich S, Su J, Ranta F, Wittekindt OH, Ris F, Rosler M, Gerlach U, Heitzmann D, Warth R, Lang F: Effects of I (Ks) channel inhibitors in insulin-secreting INS-1 cells. Pflugers Arch. 2005 Dec;451(3):428-36. 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. |
2(0,0,0,2) |