Ca2+-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 (I_Ca,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 a voltage clamp test. We also studied the linear relationship between the rising rate of the Ca²⁺ transients and the peak trigger I_Ca,L. The model results suggest that this relationship is the indirect result of 2^nd-order RyR activation dynamics, filtered by fluorescent indicator dye.