Analysis of calcium-induced calcium release in cardiac sarcoplasmic reticulum vesicles using models derived from...

The planar lipid bilayer and vesicle release experiments are two alternative approaches used to study the function of the ryanodine receptor (RyR) channel at the subcellular level. In this work, we combine models of gating (Zahradníková and Zahradník, Biophys. J. 71 (1996) 2996-3012) and permeation (Tinker et al., J. Gen. Physiol. 100 (1992) 495-517) of the cardiac RyR channel to simulate calcium release experiments on sarcoplasmic reticulum vesicles. The resulting model and real experimental data agreed well within the experimental scatter, confirming indistinguishable properties of the RyRC in the vesicle preparation and in the planar lipid bilayer. The previously observed differences in calcium dependencies of the release and the gating processes can be explained by binding of calcium within the RyRC conducting pore. A novel method of analysis of calcium dependence of calcium release was developed and tested. Three gating models of the RyRC, showing, respectively, an increase, no change, and a decrease in calcium sensitivity over time, were compared. The described method of analysis enabled determination of temporal changes in calcium sensitivity, giving potential for detection of the adaptation/inactivation phenomena of the RyRC in both vesicle and in situ release experiments.