Hook, line and sinker: adult zebrafish offer a valid model to study mammalian cardiac contractile mechanics.

Abstract

On a beat-to-beat basis, cardiac contractile function is driven by a multifaceted and dynamic process that is regulated by both intrinsic (e.g. mechanical loading) and extrinsic (e.g. neuro-hormonal) factors (de Tombe et al. 2010). Specifically, the level of contractile activation of adult mammalian cardiomyocytes is modulated by the magnitude of the Ca2+ transient, the dynamic activation–relaxation kinetic response of the sarcomere to activator Ca2+ and the responsiveness of the myofilament to Ca2+, the last of which is dependent on sarcomere length and is a primary mediator of the Frank–Starling response. While transgenic mouse models have provided important insight into the molecular mechanisms underlying cardiac contractile function in health and disease, they are associated with high cost and relatively long generation times. Recently, the zebrafish has emerged as a promising model for the study of cardiac structure–function relationships, due to short generation times, ease of genetic manipulation and low cost. While multiple studies have characterized zebrafish cardiac electrophysiology, Ca2+ dynamics and myofilament mechanical function, it remains unclear whether the cardiac contractile structure–function relationship of adult zebrafish is comparable to that of the mammalian system.