TY - JOUR T1 - Numerical Analysis of Ca2+ Signaling in Rat Ventricular Myocytes with Realistic Transverse-Axial Tubular Geometry and Inhibited Sarcoplasmic Reticulum A1 - Cheng, Yuhui A1 - Yu, Zeyun A1 - Hoshijima, Masahiko A1 - Holst, Michael J. A1 - McCulloch, Andrew D. A1 - McCammon, J. Andrew A1 - Michailova, Anushka P. Y1 - 2010/10/28 N2 - Author Summary In cardiac muscle cells, calcium (Ca2+) is best known for its role in contraction activation. A remarkable amount of quantitative data on cardiac cell structure, ion-transporting protein distributions and intracellular Ca2+ dynamics has been accumulated. Various alterations in the protein distributions or cell ultra-structure are now recognized to be the primary mechanisms of cardiac dysfunction in a diverse range of common pathologies including cardiac arrhythmias and hypertrophy. Using a 3-D computational model, incorporating more realistic transverse-axial t-tubule geometry and considering geometric irregularities and inhomogeneities in the distribution of ion-transporting proteins, we analyze several important spatial and temporal features of Ca2+ signaling in rat ventricular myocytes. This study demonstrates that the computational models could serve as powerful tools for prediction and analyses of how the Ca2+ dynamics and cardiac excitation-contraction coupling are regulated under normal conditions or certain pathologies. The use of computational and mathematical approaches will help also to better understand aspects of cell functions that are not currently amenable to experimental investigation. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 6 IS - 10 UR - https://doi.org/10.1371/journal.pcbi.1000972 SP - e1000972 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1000972 ER -