A model of sarcolemmal Ca2+ current and cytosolic Ca2+ transient in a rat ventricular cell

We have developed a mathematical model for the sarcolemmal Ca²⁺ current and the cytosolic Ca²⁺ transient in a rat ventricular myocyte based on recent experimental data. A lumped fluid-compartment model is developed that includes separate multi-state kinetic models for the L-type Ca²⁺ current (I_Ca,L) of the sarcolemma (SL) and the ryanodine-sensitive Ca²⁺ current (I_release) of the sarcoplasmic reticulum (SR). The cleft space volume between the SL and SR is divided into three sub-compartments and material balances for Ca²⁺ are provided for each compartment. A relatively large cytosolic compartment containing Ca²⁺ buffers (calmodulin, troponin) is also provided and the SR is modeled in terms of individual longitudinal uptake, transfer and release compartments. Calcium buffering is also provided in the Ca²⁺ release compartment (calsequestrin). The lumped model can accurately simulate the family of I_Ca,L waveforms and associated cytosolic Ca²⁺ transients from voltage clamp studies of the isolated rat ventricular cell. Implicit in the model is a description of calcium-induced calcium-release (CICR). The model also simulates a number of important features of excitation-contraction coupling including: (a). graded Ca²⁺-release, (b). voltage- and Ca²⁺-dependent inactivation of I_Ca,L, and (c). Ca²⁺-dependent inactivation of I_release