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-cells: Role of the Plasma Membrane and Intracellular Stores
1 Department of Medicine, University of Chicago, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: l-philipson{at}uchicago.edu.
We have developed a detailed mathematical model of ionic flux in
-cells that includes the most essential channels and pumps in the plasma membrane. This model is coupled to the equations describing Ca2+, inositol 1,4,5-trisphosphate (IP3), ATP and Na+ homeostasis, including the uptake and release of Ca2+ by the endoplasmic reticulum (ER). In our model, metabolically derived ATP activates inward Ca2+ flux by regulation of ATP-sensitive K+ channels and depolarization of the plasma membrane. Results from the simulations support the hypothesis that intracellular Na+ and Ca2+ in the ER can be the main variables driving both fast (2-7 osc/min) and slow Cai oscillations (0.3-0.9 osc/min), and that the effect of IP3 on Ca2+ leak from the ER contributes to the pattern of slow calcium oscillations. Simulations also show that filling the ER Ca2+ stores leads to faster electrical bursting and Ca2+ oscillations. Specific Ca2+ oscillations in isolated
-cell lines can also be simulated.
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