|ZFIN ID: ZDB-PUB-100420-30|
High-resolution cardiovascular function confirms functional orthology of myocardial contractility pathways in zebrafish
Shin, J.T., Pomerantsev, E.V., Mably, J.D., and MacRae, C.A.
|Source:||Physiological Genomics 42(2): 300-309 (Journal)|
|Registered Authors:||Mably, John, MacRae, Calum A., Shin, Jordan|
|Keywords:||zebrafish, heart, inotropy|
|PubMed:||20388839 Full text @ Physiol. Genomics|
Shin, J.T., Pomerantsev, E.V., Mably, J.D., and MacRae, C.A. (2010) High-resolution cardiovascular function confirms functional orthology of myocardial contractility pathways in zebrafish. Physiological Genomics. 42(2):300-309.
ABSTRACTPhenotype-driven screens in larval zebrafish have transformed our understanding of the molecular basis of cardiovascular development. Screens to define the genetic determinants of physiologic phenotypes have been slow to materialize as a result of the limited number of validated in vivo assays with relevant dynamic range. To enable rigorous assessment of cardiovascular physiology in living zebrafish embryos, we developed a suite of software tools for the analysis of high-speed video-microscopic images and validated these using established cardiomyopathy models in zebrafish as well as modulation of the nitric oxide (NO) pathway. Quantitative analysis in wild type (WT) fish exposed to nitric oxide or in a zebrafish model of dilated cardiomyopathy demonstrated that these tools detect significant differences in ventricular chamber size, ventricular performance, and aortic flow velocity zebrafish embryos across a large dynamic range. These methods also were able to establish the effects of the classic pharmacological agents isoproterenol, ouabain and verapamil on cardiovascular physiology in zebrafish embryos. Sequence conservation between zebrafish and mammals of key amino acids in the pharmacological targets of these agents correlated with the functional orthology of the physiologic response. These data provide evidence that the quantitative evaluation of subtle physiologic differences in zebrafish can be accomplished at a resolution and with a dynamic range comparable to that achieved in mammals, and provides a mechanism for genetic and small molecule dissection of functional pathways in this model organism.