Ca/sup 2+/-induced calcium-release in a rat ventricular cell - a model study

A computer model is developed for the characterization of Ca/sup 2+/-induced calcium release (CICR) from the sarcoplasmic reticulum (SR) in the rat ventricular cell. The fluid compartment model is configured to describe the trigger Ca/sup 2+/ influx (I/sub Ca,L/) through the membrane of the sarcolemma (SL); the diffusion of Ca/sup 2+/ throughout a small cleft space, which is located between the SL and the junctional sarcoplasmic reticulum (jSR); and a distribution of five ryanodine (Ry)-sensitive Ca/sup 2+/ release channels called the "Ca/sup 2+/-release complex". Each Ry-receptor controlled channel (or RyR channel) is characterized by a 4-state Markovian kinetic scheme. Two Ca/sup 2+/ ions are required to bind to RyR for channel activation, and one Ca/sup 2+/ ion is required for channel inactivation. The model provides both sufficient Ca/sup 2+/-release gain and graded release behavior. The complete model is used to simulate the whole-cell Ca/sup 2+/ transient data, evoked in a voltage clamp test. We also studied the linear relationship between the rising rate of the Ca/sup 2+/ transients and the peak trigger I/sub Ca,L/. The model results suggest that this relationship is the indirect result of 2/sup nd/-order RyR activation dynamics, filtered by fluorescent indicator dye.