Location: Clark 110 Homewood Campus
Title: Searching High and Low: Incorporating various levels of structure and function to more realistically model cardiac arrhythmias
Abstract: Myocytes and fibroblasts are the two major cell types in healthy mammalian myocardium. Although myocytes are primarily responsible for the mechanical function and occupy most of the tissue volume, fibroblasts outnumber myocytes by a ratio of approximately 3:2. In canine left ventricle, fibroblasts have been identified in the immediate vicinity of each myocyte. Gap junctional proteins, connexins 43 (Cx43) and 45 (Cx45), are expressed by cardiac fibroblasts, and dye coupling from fibroblasts to atrial and ventricular myocytes has been demonstrated, suggesting that myocytes and fibroblasts are functionally coupled by gap junctions and may interact via two-way electrotonic signaling. Studies involving electrophysiological coupling have shown that when variable numbers of myofibroblasts were cultured over sheets of neonatal myocytes, recordings from myocytes showed that the rate of action potential depolarization and conduction velocity decreased with increasing density of myofibroblasts. Previous work had shown that mechanosensitive atrial or sinoatrial fibroblasts were also coupled electrotonically to adjacent myocytes Thus, electrotonic coupling can occur in vivo as well as in vitro settings. In addition to having potentially significant effects upon the electrophysiological responses of the myocyte and the local conduction environment, the role of fibroblast membrane kinetics and fibroblast-myocyte coupling in the pathophysiological setting of myocardial fibrosis remains poorly understood. This presentation will offer an overview of a pair of studies whose goal is to elucidate the effects of fibroblast-myocyte interactions on conduction and excitation at the tissue and cellular levels, respectively.
Laboratory: Computational Cardiac Electrophysiology Lab -- Dr. Trayanova
