Ca-induced Calcium-Release in a Rat Ventricular Cell ---- A Model Study

A computer model is developed for the characterization of Ca2+-induced calcium release (CICR) from the sarcoplasmic reticulum (SR) in the rat ventricular cell. The fluid compartment model is configured to describe the trigger Ca2+ influx (ICa,L) through the membrane of the sarcolemma (SL); the diffusion of Ca2+ 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 Ca2+ release channels called the "Ca2+-release complex". Each Ry-receptor controlled channel (or RyR channel) is characterized by a 4-state Markovian kinetic scheme. Two Ca2+ ions are required to bind to RyR for channel activation, and one Ca2+ ion is required for channel inactivation. The model provides both sufficient Ca2+-release gain and graded release behavior. The complete model is used to simulate the whole-cell Ca2+ transient data, evoked in voltage clamp test. We also studied the linear relationship between the rising rate of the Ca2+ transients and the peak trigger ICa,L. The model results suggest that this relationship is the indirect result of 2nd-order RyR activation dynamics, filtered by fluorescent indicator dye.