TY - UNPB
T1 - Accounting for near-normal glucose sensitivity in Kir6.2[AAA] transgenic mice
AU - Tsaneva-Atanasova, KT
AU - Sherman, Arthur
PY - 2009
Y1 - 2009
N2 - Kir6.2[AAA] transgenic mouse islets exhibit mosaicism such that approximately
70% of the -cells have non-functional ATP-sensitive potassium (KATP ) channels,
whereas the remainder have normal KATP function (1, 2). In spite of this drastic
reduction, the glucose dose-response curve is only shifted by about 2 mM. We use
a previously published mathematical model (3), 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 up-regulate 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.
AB - Kir6.2[AAA] transgenic mouse islets exhibit mosaicism such that approximately
70% of the -cells have non-functional ATP-sensitive potassium (KATP ) channels,
whereas the remainder have normal KATP function (1, 2). In spite of this drastic
reduction, the glucose dose-response curve is only shifted by about 2 mM. We use
a previously published mathematical model (3), 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 up-regulate 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.
KW - bifurcation theory
KW - diffusion
KW - mathematical model
KW - synchronization
KW - coupled oscillators
M3 - Working paper
BT - Accounting for near-normal glucose sensitivity in Kir6.2[AAA] transgenic mice
ER -