Functional Cardiac Phenotypes in Zebrafish Caldesmon Morphants
A Digital Motion Analysis
All vertebrates have a closed cardiovascular system in which the blood cells circulate through the whole body within vessels, return to the atrium via the sinus venosus, and are pumped predominantly by the ventricle through the outflow tract to the whole body. As the pacemaker the sinus venosus is the first to contract. A wave of muscle contraction is then propagated up to the ventricle through the atrium. To maintain the forward blood flow, the atrium does not relax until the ventricle contracts. The valves develop at the boundaries of chambers. Contraction proceeds in a coordinated fashion with the valves opening and closing to prevent the retrograde flow of blood. The normal heart beats regularly and coordinately with a 1:1 ratio of atrial to ventricular beats. There is a reciprocal relationship between structural and functional alterations of cardiovascular systems. Characterization of both functional and structural phenotypes is important for determination of the effects of a morpholino gene knockdown. The cardiovascular system is particularly amenable for screening in transparent zebrafish embryos because the heart and blood vessels are prominent and their function is easily examined.
In our previous studies, we have investigated structural cardiac1 and vascular2 alterations of zebrafish caldesmon morphants (CaD-MOs), and the molecular mechanism of the cardiac failure is also explored.3 Here we show functional cardiac phenotypes in CaD-MOs. In contrast to control embryos (online-only Data Supplement Movie I), the knockdown of caldesmon affects the normal function of the heart involving the contractility and the rhythmicity of the heart. Abnormalities of the rhythmicity of the morphant hearts manifest primarily as defects in the rate, rhythm, or conduction of the cardiac impulse. A defect of contractility is reflected by uncoordinated or weak contraction or both. The morphants show complex cardiac phenotypes with both abnormalities of contractility and rhythmicity (online-only Data Supplement Movies II through VI). The still frames corresponding to each Movie are shown in the Figure. The findings suggest that caldesmon is required for proper cardiac function and provide additional support for the notion that this molecule is essential for cardiac development. As for the clinical relevance of these findings, they may be helpful in designing future therapeutic strategies in the regeneration of cardiac damage.
↵*Dr Willemsen and Dr Kros contributed equally to this work.