Effects of extracellular calcium on electrical bursting and intracellular and luminal calcium oscillations in insulin secreting pancreatic beta-cells

Effects of extracellular calcium on electrical bursting and intracellular and luminal calcium oscillations in insulin secreting pancreatic beta-cells

Model Status

This model is able to reproduce the figures presented in the Chay 1997 paper and this version has a PCEnv session file associated with it. The value for the variable 'Ca_o' in the component 'calcium_current' can be altered to 0, 2.5, 5 or 7.5 mM to reproduce figures 5 a,b,c,d, respectively.

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Model Structure

When exposed to a threshold concentration of glucose, pancreatic beta-cells exhibit a complicated pattern of electrical activity. Bursts of action potential spikes (the "active" phase) are observed, separated by a "silent" phase of membrane repolarisation. At even higher glucose concentrations, continuous action potentials are seen. This electrical activity is influenced by the extracellular calcium concentration ([Ca2+]o). Specifically, in a mouse pancreatic beta-cell in a medium containing a moderate amount of glucose, an increase in [Ca2+]o lowers the repolarisation potential, raises the plateau potential and shortens the spike and plateau durations. The mechanisms underlying these affects are not well understood.

In her 1997 paper, Teresa Chay elucidates the role of extracellular calcium concentration in influencing electrical activity, intracellular calcium concentration, and the luminal calcium concentration in the intracellular calcium store of pancreatic beta-cells. She studies the extracellular calcium effect using a mathematical model which includes seven currents across the plasma membrane and two calcium fluxes across the membrane of the endoplasmic reticulum (ER) (see the figure below).

The complete original paper reference is cited below:

Effects of extracellular Calcium on Electrical Bursting and Intracellular and Luminal Calcium Oscillations in Insulin Secreting Pancreatic Beta-Cells, Teresa Ree Chay, 1997, Biophysical Journal , 73, 1673-1688. PubMed ID: 9284334

The raw CellML description of the model can be downloaded in various formats as described in

A schematic representation of the current and fluxes captured by the Chay 1997 pancreatic beta-cell model. This diagram shows the plasma membrane currents associated with burst and spike oscillations: the fast current, Ifast; the calcium current, I Ca2+ ; the cationic nonselective inward current, INS; the delayed-rectifying K+ current, IK(dr), the calcium-sensitive K+ current, IK(Ca); the ATP-sensitive K+ current, IK(ATP); and the Na+ leak current, INa(L). The ER intracellular Ca2+ store is also shown with its associated transmembrane calcium fluxes: calcium release, Jrel; and calcium uptake by the Ca2+-ATPase, Jpump.