Characterisation of sulphonylurea and ATP-regulated K+ channels in rat pancreatic A-cells

• DOI: 10.1007/s004249900076
• Publication Date: 2015-10-28T01:57:45Z
• Authors: K. Bokvist; H.L. Olsen; M. Høy; C.F. Gotfredsen; W.F. Holmes; K. Buschard; P. Rorsman; J. Gromada
• Keywords: Diazoxide; Cromakalim; Tolbutamide; Pinacidil; Sulfonylurea receptor; Kir6.2; ATP-sensitive potassium channel

We have monitored whole-cell and single channel ATP-sensitive K+ (KATP) currents in isolated rat glucagon-secreting pancreatic A-cells. Tolbutamide produced a concentration-dependent decrease in the whole-cell KATP conductance (Ki = 6 microM) and initiated action potential firing. The K+ channel opener diazoxide, but not cromakalim or pinacidil, inhibited electrical activity and increased the whole-cell K+ conductance fourfold. ATP applied to the intracellular face of the membrane inhibited KATP channel activity with a Ki of 17 microM, an effect that could be counteracted by Mg-ADP and Mg-GDP. GTP and UTP did not affect KATP channel activity. Phosphatidylinositol 4,5-bisphosphate activated KATP channels inhibited by ATP after a delay of 90 s. In situ hybridisation demonstrated the expression of the mRNA encoding KATP channel subunits Kir6.2 and SUR1 but not Kir6.1 and SUR2. We conclude that rat pancreatic A-cells express KATP channels with the nucleotide-, sulphonylurea- and K+ channel-opener sensitivities expected for a channel formed by Kir6.2 and SUR1 subunits.