Analysis of calcium-induced calcium release in cardiac sarcoplasmic reticulum vesicles using models derived from single-channel data

The planar lipid bilayer and vesicle release experiments are two alternativ e approaches used to study the function of the ryanodine receptor (RyR) cha nnel at the subcellular level. In this work, we combine models of gating (Z ahradnikova and Zahradnik, Biophys. J. 71 (1996) 2996-3012) and permeation (Tinker et al., J. Gen. Physiol. 100 (1992) 495-517) of the cardiac RyR cha nnel to simulate calcium release experiments on sarcoplasmic reticulum vesi cles. 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 Bating models of the RyRC, showing, respect ively, an increase, no change, and a decrease in calcium sensitivity over t ime, 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 i n situ release experiments. (C) 1999 Elsevier Science B.V. All rights reser ved.