Accounting for Near-Normal Glucose Sensitivity in K(ir)6.2[AAA] Transgenic Mice

作者：Tsaneva Atanasova Krasimira; Sherman Arthur^*

来源：Biophysical Journal, 2009, 97(9): 2409-2418.

DOI：10.1016/j.bpj.2009.07.060

K(ir)6.2[AAA] transgenic mouse islets exhibit mosaicism such that similar to 70% of the beta-cells have nonfunctional ATP-sensitive potassium (K-ATP) channels, whereas the remainder have normal KATP function. Despite this drastic reduction, the glucose dose-response curve is only shifted by similar to 2 mM. We use a previously published mathematical model, in which K-ATP conductance is increased by rises in cytosolic calcium through indirect effects on metabolism, to investigate how cells could compensate for the loss of K-ATP conductance. Compensation is favored by the assumption that only a small fraction of K-ATP 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.

• 出版日期2009-11-4