A membrane potential model with counterions for cytosolic calcium oscillations

An initial model has been proposed to describe a mechanism for cytosolic calcium oscillations [Jafri MS. Vajda S. Pasik P. Gillo B. (1992) A membrane model for cytosolic calcium oscillations: a study using Xenopus oocytes. Biophys. J., 63, 235-246]. In this paper we extend our original model to include the effects of counterion movement into the ER in response to calcium release. This produces smoother oscillations over a wider parameter range. We have lowered the endoplasmic reticulum (ER) intraluminal free calcium concentration and shown that the oscillations can occur at lower ER membrane potentials, consistent with physiological values. The improved model is then tested with two representative paradigms that are currently under investigation by many researchers. The model predicts that the reduction of the ER calcium pump (Ca-ATPase) rate can cause the termination of cytosolic calcium oscillations in an active cell, and induce oscillations in a resting cell. This result is consistent with experiments with thapsigargin, a Ca-ATPase activity inhibitor. In addition, we simulate the latency period for the response to the application of agonist and offer a plausible explanation for it. Our mathematical model is currently the only model that formulates the contributions of calcium binding proteins, ER membrane potential, ER counterion movements, and distinct calcium pump populations, and describes their effects on cytosolic calcium oscillations.