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Accounting for Near-Normal Glucose Sensitivity in Kir6.2[AAA] Transgenic Mice

By Krasimira Tsaneva-Atanasova and Arthur Sherman

Abstract

AbstractKir6.2[AAA] transgenic mouse islets exhibit mosaicism such that ∼70% of the β-cells have nonfunctional ATP-sensitive potassium (KATP) channels, whereas the remainder have normal KATP function. Despite this drastic reduction, the glucose dose-response curve is only shifted by ∼2 mM. We use a previously published mathematical model, in which KATP conductance is increased by rises in cytosolic calcium through indirect effects on metabolism, to investigate how cells could compensate for the loss of KATP conductance. Compensation is favored by the assumption that only a small fraction of KATP channels are open during oscillations, which renders it easy to upregulate the open fraction via a modest elevation of calcium. We show further that strong gap-junctional coupling of both membrane potential and calcium is needed to overcome the stark heterogeneity of cell properties in these mosaic islets

Publisher: Biophysical Society. Published by Elsevier Inc.
Year: 2009
DOI identifier: 10.1016/j.bpj.2009.07.060
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