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Spatial-temporal Ca^2+ dynamics due to Ca^2+ release, buffering, and reuptaking plays a central role in studying excitation–contraction (E–C) coupling in both normal and diseased cardiac myocytes. In this paper, we employ two numerical methods, namely, the meshless method and the finite element method, to model such Ca^2+ behaviors by solving a nonlinear system of reaction–diffusion partial differential equations at two scales. In particular, a subcellular model containing several realistic transverse tubules (or t-tubules) is investigated and assumed to reside at different locations relative to the cell membrane. To this end, the Ca^2+ concentration calculated from the whole-cell modeling is adopted as part of the boundary constraint in the subcellular model. The preliminary simulations show that Ca^2+ concentration changes in ventricular myocytes are mainly influenced by calcium release from t-tubules. [ABSTRACT FROM AUTHOR]

To investigate the mechanisms regulating excitation-metabolic coupling in rabbit epicardial, midmyocardial, and endocardial ventricular myocytes we extended the LabHEART model (Puglisi JL and Bers DM. Am J Physiol Cell Physiol 281: C2049-C2060, 2001). We incorporated equations for Ca2+ and Mg2+ buffering by ATP and ADP, equations for nucleotide regulation of ATP-sensitive K+ channel and L-type Ca2+ channel, Na+-K+-ATPase, and sarcolemmal and sarcoplasmic Ca2+-ATPases, and equations describing the basic pathways (creatine and adenylate kinase reactions) known to communicate the flux changes generated by intracellular ATPases. Under normal conditions and during 20 mm of ischemia, the three regions were characterized by different INa, Ito, IKr, IKs, and IKp channel properties. The results indicate that the ATP-sensitive K+ channel is activated by the smallest reduction in ATP in epicardial cells and largest in endocardial cells when cytosolic ADP, AMP, PCr, Cr, Pi, total Mg2+, Na+, K+, Ca2+, and pH diastolic levels are normal. The model predicts that only KATP ionophore (Kir6.2 subunit) and not the regulatory subunit (SUR2A) might differ from endocardium to epicardium. The analysis suggests that during ischemia, the inhomogeneous accumulation of the metabolites in the tissue sublayers may alter in a very irregular manner the KATP channel opening through metabolic interactions with the endogenous PI cascade (PIP2, PIP) that in turn may cause differential action potential shortening among the ventricular myocyte subtypes. The model predictions are in qualitative agreement with experimental data measured under normal and ischemic conditions in rabbit ventricular myocytes. [ABSTRACT FROM AUTHOR]