Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation
Formulations for all currents and fluxes were based either directly (gray) or indirectly (white) on undiseased or nonfailing human experimental data. Model includes four compartments: 1) bulk myoplasm (myo), 2) junctional sarcoplasmic reticulum (JSR), 3) network sarcoplasmic reticulum (NSR), and 4) subspace (SS), representing the space near the T-tubules. Currents into the myoplasm: Na+ current (INa; representing both fast and late components), transient outward K+ current (Ito), rapid delayed rectifier K+ current (IKr), slow delayed rectifier K+ current (IKs), inward rectifier K+ current (IK1), 80% of Na+/Ca2+ exchange current (INaCa,i), Na+/K+ pump current (INaK), background currents (INab, ICab, and IKb), and sarcolemmal Ca2+ pump current (IpCa). Currents into subspace: L-type Ca2+ current (ICaL, with Na+ and K+ components ICaNa, ICaK), and 20% of Na+/Ca2+ exchange current (INaCa,ss). Ionic fluxes: Ca2+ through ryanodine receptor (Jrel), NSR to JSR Ca2+ translocation (Jtr), Ca2+ uptake into NSR via SERCA2a/PLB (Jup; PLB - phospholamban), diffusion fluxes from subspace to myoplasm (Jdiff,Na, Jdiff,Ca, and Jdiff,K). Ca2+ Buffers: calmodulin (CMDN), troponin (TRPN), calsequestrin (CSQN), anionic SR binding sites for Ca2+ (BSR), anionic sarcolemmal binding sites for Ca2+ (BSL). Ca2+/calmodulin-dependent protein kinase II (CaMK) and its targets are labeled.