Generation of Slow Calcium oscillations in Spatial Cell Models Driven by Store Operated Calcium Entry

• Calcium signaling is involved in many cellular processes ranging from fertilization to apoptosis. We have created two general mathematical models to simulate calcium transport between the endoplasmic reticulum (ER), the cytosol and the extracellular environment. Active in this process is inositol-1,4,5-trisphosphate (InsP3). The behavior of the changes in calcium concentration was studied. The first model is compartmental and uses ordinary differential equations. The second one is a spatial model, which uses partial differential equations. The tools used in constructing these models were MATLAB and Virtual Cell. Store operated calcium entry can be observed in experiments with living cells when the sarco(endo)plasmic reticulum calcium-ATPase (SERCA) pumps are blocked by cyclopiazonic acid (CPA) or thapsigargin. We have developed a phenomenological model of store operated calcium channels (SOC). This model involves a diffusible messenger that leaves the ER and binds to a channel in the plasma membrane. Many parameters in the models are not fully known. A basic assumption is that the parameters can be estimated from the fact that a cell at rest has an almost constant level of calcium. Results from both the compartmental and the spatial simulations show that InsP3 can cause the cytosolic calcium level to oscillate at frequencies between 1 and 5 mHz. Experimental studies have shown than calcium oscillations in this frequency range are present in renal cells. The SERCA blocking simulations show good similarity with experimental results. The results also show that the high surface-to-volume ratio of the ER is important for causing oscillations.

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NATURVETENSKAP  -- Biologi -- Biofysik (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biophysics (hsv//eng)

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