<i>Nkx2.5</i> is essential to establish normal heart rate variability in the zebrafish embryo

Abstract

Heart rate variability (HRV) has become an important clinical marker of cardiovascular health and a research measure for the study of the cardiac conduction system and its autonomic controls. While the zebrafish (<i>Danio rerio</i>) is an ideal vertebrate model for understanding heart development, HRV has only recently been investigated in this system. We have previously demonstrated that <i>nkx2.5</i> and <i>nkx2.7</i>, two homologues of <i>Nkx2-5</i> expressed in zebrafish cardiomyocytes, play vital roles in maintaining cardiac chamber-specific characteristics. Given observed defects in ventricular and atrial chamber identities in <i>nkx2.5^-/-</i> embryos coupled with conduction system abnormalities in murine models of <i>Nkx2.5</i> insufficiency, we postulated that reduced HRV would serve as a marker of poor cardiac health in <i>nkx2.5</i> mutants and in other zebrafish models of human congenital heart disease. Using live video image acquisition, we derived beat-to-beat intervals to compare HRV in wild-type and <i>nkx2.5^-/-</i> embryos. Our data illustrate that the <i>nkx2.5</i> loss-of-function model exhibits increased heart rate and decreased HRV when compared with wild type during embryogenesis. These findings validate HRV analysis as a useful quantitative tool for assessment of cardiac health in zebrafish and underscore the importance of <i>nkx2.5</i> in maintaining normal heart rate and HRV during early conduction system development.