Adrenaline-induced hyperpolarization of mouse pancreatic islet cells is mediated by G protein-gated inwardly rectifying potassium (GIRK) channels.
Insulin secretion inhibitors (ISI) such as adrenaline and somatostatin act on the pancreatic beta-cell by a number of mechanisms, one of which is plasma membrane hyperpolarization. Despite the ample evidence for this effect, the principal underlying channels have not been identified thus far. The G protein-gated inwardly rectifying potassium (Kir3.x/GIRK) channels, which are responsible for hyperpolarization in other excitable tissues, are likely candidates. In this paper, we show that GIRK channels are expressed and functional in mouse pancreatic islet cells. Reverse transcription polymerase chain reaction analysis revealed all four GIRK gene products in islet tissue. Immunofluorescent labeling of pancreatic sections demonstrated exclusive islet localization of all GIRK subunits, in part within insulin-expressing cells. Using the whole-cell configuration of the patch clamp technique, we found that the application of tertiapin-Q, a selective inhibitor of the GIRK channels, abolishes adrenaline-mediated inward currents and strongly attenuates adrenaline-induced hyperpolarization in a reversible manner. These results imply that GIRK channels are responsible for a major part of the electrical response to adrenaline in islet cells and suggest a role for these channels in pancreatic physiology.
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel.
Shachar
S
Iwanir
Eitan
E
Reuveny
D000818:Animals; D004594:Electrophysiology; D004837:Epinephrine / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D018408:Patch-Clamp Techniques; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D012313:RNA; D004837:Epinephrine