Ca2+-Induced Calcium-Release in a Rat Ventricular Cell --- A Model Study

摘要

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