Inwardly rectifying Kir2.1 currents in human β-cells control electrical activity: characterisation and mathematical modelling

Biochemical and Biophysical Research Communications
Michela RizMorten Gram Pedersen

Abstract

Pancreatic β-cells fire action potentials as do cardiac cells and neurons, and electrical activity plays a central role in glucose-stimulated insulin secretion, which is disturbed in diabetes. The inwardly rectifying Kir2.1 potassium channels (KCNJ2 gene) control cardiac electrical activity by stabilising the interspike interval. Loss-of-function abnormalities in cardiac Kir2.1 currents can lead to the long QT syndrome and alterations of cardiac excitability, and patients with some forms of long QT syndrome suffer from over-secretion of insulin, hyperinsulinemia and symptomatic hypoglycemia. The KCNJ2 gene is also expressed in human pancreatic islets, and we show that functional Kir2.1 currents are present in human β-cells. We characterised the human Kir2.1 β-cell current, and included it in a recent mathematical model of electrical activity in human β-cells. Based on our simulations we propose that Kir2.1 currents control the interspike interval, and predict that blocking Kir2.1 channels increases the action potential frequency, which should augment the rate of insulin secretion. Vice versa, the model suggests that hyperactive Kir2.1 channels may lead to reduced insulin secretion. Our findings provide a putative link between i...Continue Reading

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Citations

Dec 8, 2017·Physiological Reviews·Patrik Rorsman, Frances M Ashcroft
Dec 14, 2019·International Journal for Numerical Methods in Biomedical Engineering·Gerardo J Félix-MartínezAmparo Gil
Jun 17, 2020·Molecular & Cellular Proteomics : MCP·Sung-Soo ParkJean-François Rual
Nov 14, 2015·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Christian CherubiniAlessandro Loppini
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Sung-Soo ParkJean-François Rual

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