Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation

doi:10.1371/journal.pcbi.1002061

Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation

Figure 5

Schematic diagram of human ventricular myocyte model.

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 (I_Na; representing both fast and late components), transient outward K⁺ current (I_to), rapid delayed rectifier K⁺ current (I_Kr), slow delayed rectifier K⁺ current (I_Ks), inward rectifier K⁺ current (I_K1), 80% of Na⁺/Ca²⁺ exchange current (I_NaCa,i), Na⁺/K⁺ pump current (I_NaK), background currents (I_Nab, I_Cab, and I_Kb), and sarcolemmal Ca²⁺ pump current (I_pCa). Currents into subspace: L-type Ca²⁺ current (I_CaL, with Na⁺ and K⁺ components I_CaNa, I_CaK), and 20% of Na⁺/Ca²⁺ exchange current (I_NaCa,ss). Ionic fluxes: Ca²⁺ through ryanodine receptor (J_rel), NSR to JSR Ca²⁺ translocation (J_tr), Ca²⁺ uptake into NSR via SERCA2a/PLB (J_up; PLB - phospholamban), diffusion fluxes from subspace to myoplasm (J_diff,Na, J_diff,Ca, and J_diff,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.

doi: https://doi.org/10.1371/journal.pcbi.1002061.g005