A comprehensive mathematical model of ventricular and sinoatrial node cells successfully reconstructs excitation-contraction coupling and serves as a predictive tool for generating testable hypotheses regarding ionic current systems.
Individual ion channels or exchangers are described with a common set of equations for both the sinoatrial node pacemaker and ventricular cells. New experimental data are included, such as the new kinetics of the inward rectifier K+ channel, delayed rectifier K+ channel, and sustained inward current. The gating model of Shirokov et al. (J Gen Physiol 102: 1005-1030, 1993) is used for both the fast Na+ and L-type Ca2+ channels. When combined with a contraction model (Negroni and Lascano: J Mol Cell Cardiol 28: 915-929, 1996), the experimental staircase phenomenon of contraction is reconstructed. The modulation of the action potential by varying the external Ca2+ and K+ concentrations is well simulated. The conductance of I(CaL) dominates membrane conductance during the action potential so that an artificial increase of I(to), I(Kr), I(Ks), or I(KATP) magnifies I(CaL) amplitude. Repolarizing current is provided sequentially by I(Ks), I(Kr), and I(K1). Depression of ATP production results in the shortening of action potential through the activation of I(KATP). The ratio of Ca2+ released from SR over Ca2+ entering via I(CaL) (Ca2+ gain = approximately 15) in excitation-contraction coupling well agrees with the experimental data. The model serves as a predictive tool in generating testable hypotheses.
Matsuoka et al. (Wed,) studied this question.