As science uncovers more information about cellular processes at the molecular level, the task of integrating such findings into the physiological system becomes increasingly pertinent. Many experiments in cellular cardiac electrophysiology are conducted at a molecular level and need to be integrated into the context of the whole cell, the multicellular tissue, and the heart. Biophysically based computer models that integrate findings on the molecular level to predict macroscopic results are useful in accomplishing this task. Here we propose to construct molecular level models of ion channels that generate the action potential in ventricular myocytes. These models will provide insight into the roles of these channels in action potential generation in both healthy and diseased states. Moreover, this insight will give a mechanistic basis for the treatment of cardiac arrhythmias and prevention of sudden cardiac death.
| Silva, Jonathan R; Rudy, Yoram (2010) Multi-scale electrophysiology modeling: from atom to organ. J Gen Physiol 135:575-81 |
| Silva, Jonathan R; Pan, Hua; Wu, Dick et al. (2009) A multiscale model linking ion-channel molecular dynamics and electrostatics to the cardiac action potential. Proc Natl Acad Sci U S A 106:11102-6 |
| Silva, Jonathan; Rudy, Yoram (2005) Subunit interaction determines IKs participation in cardiac repolarization and repolarization reserve. Circulation 112:1384-91 |
| Silva, Jonathan; Rudy, Yoram (2003) Mechanism of pacemaking in I(K1)-downregulated myocytes. Circ Res 92:261-3 |
