Cardiac conduction is required to preserve cardiac chamber morphology

• DOI: 10.1073/pnas.0909432107
• Publication Date: 2010-07-31T02:12:54Z
• Authors: Neil C. Chi; Markus Bussen; Koroboshka Brand-...; Chunhua Ding; Jeffrey E. Olgin; Robin M. Shaw; Gail R. Martin; Didier Y. R. Stai...
• Keywords: Heart development

Electrical cardiac forces have been previously hypothesized to play a significant role in morphogenesis and remodeling. In response electrical forces, cultured cardiomyocytes rearrange their cytoskeletal structure modify gene expression profile. To translate such vitro data the intact heart, we used collection of zebrafish mutants transgenics investigate whether conduction could influence vivo independent contractile forces. We show that mutant dco s226 develops heart failure interrupted following uncoordinated ventricular contraction. Using optical mapping/calcium imaging, determined phenotype was primarily due aberrant conduction. Because contraction intracardiac hemodynamic can also development, further analyzed noncontractile hearts observed disorganized affect cardiomyocyte morphology subsequent absence or flow. By positional cloning, found encodes Gja3/Cx46, gap junction protein not implicated formation function. Detailed analysis mouse Cx46 revealed presence defects frequently associated with human failure. Overall, these studies indicate are required preserve chamber may act as key epigenetic factor