Calcium Oscillations driving an excitable membrane: Hysteresis and Bi-stability

J.M.A.M. Kusters, A.P.R. Theuvenet, D.L. Ypey, W.P.M. van Meerwijk, J.M. Cortes and C.C.A.M. Gielen. Calcium Oscillations driving an excitable membrane: Hysteresis and Bi-stability. Biophysical Society: 51th Annual Meeting. Biophysical Journal 257A-257A Suppl. S, 2007

In normal rat kidney (NRK) fibroblasts the excitable membrane exhibits action potentials caused by an intracellular, IP3-mediated calcium oscillation (CaO). We modeled that process in detail and applied bifurcation analysis to investigate the dynamic behaviour of the model. Taking the IP3 concentration as a control parameter, the model exhibits a rich spectrum of stable and unstable states of membrane potential and cytosolic calcium, with hysteresis. The four stable states of the model correspond to previously reported growth-state dependent states of the membrane potential and CaO of NRK fibroblasts in cell culture. The hysteresis is most profound for experimentally observed parameter values of the model, suggesting a functional importance of hysteresis. The results indicate that the four growth-dependent cell states may not reflect differently differentiated cell types, but simply four different states of a single cell type, responding to changing conditions.

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