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Adrenaline-induced hyperpolarization of mouse pancreatic islet cells is mediated by G protein-gated inwardly rectifying potassium (GIRK) channels

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Abstract

Insulin secretion inhibitors (ISI) such as adrenaline and somatostatin act on the pancreatic β-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.

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Acknowledgements

We would like to thank Dr. Colin Nichols and Dr. Mike Walker for their help, and Dr. Claes Wollheim and Dr. Jun-Ichi Miyazaki for their permission to use the INS-1E and MIN-6 lines, respectively. This work was supported in part by the Minerva Foundation, the Israeli Science Foundation (ISF grant 128/05), and the Y. Leon Benoziyo Institute for Molecular Medicine.

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  1. Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel

    Shachar Iwanir & Eitan Reuveny

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  1. Shachar Iwanir
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Correspondence to Eitan Reuveny.

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Supplementary Fig. 1

Co-localization of GIRK subunits (red) and glucagon (green) in mouse pancreatic islets. Bar = 50 m (GIF 1.02 MB)

High resolution image file (TIFF 1.13 MB)

Supplementary Fig. 2

Co-localization of GIRK subunits (red) and somatostatin (green) in mouse pancreatic islets. Bar = 50 m (GIF 915 kb)

High resolution image file (TIFF 893 kb)

Supplementary Fig. 3

Co-localization of GIRK subunits (red) and pancreatic polypeptide (green) in mouse pancreatic islets. Bar = 50 m (GIF 0.97 MB)

High resolution image file (TIFF 1.01 MB)

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Iwanir, S., Reuveny, E. Adrenaline-induced hyperpolarization of mouse pancreatic islet cells is mediated by G protein-gated inwardly rectifying potassium (GIRK) channels. Pflugers Arch - Eur J Physiol 456, 1097–1108 (2008). https://doi.org/10.1007/s00424-008-0479-4

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