Ion flux dependent and independent functions of ion channels in the vertebrate heart: lessons learned from zebrafish

Abstract

Ion channels orchestrate directed flux of ions through membranes and are essential for a wide range of physiological processes including depolarization and repolarization of biomechanical activity of cells. Besides their electrophysiological functions in the heart, recent findings have demonstrated that ion channels also feature ion flux independent functions during heart development and morphogenesis. The zebrafish is a well-established animal model to decipher the genetics of cardiovascular development and disease of vertebrates. In large scale forward genetics screens, hundreds of mutant lines have been isolated with defects in cardiovascular structure and function. Detailed phenotyping of these lines and identification of the causative genetic defects revealed new insights into ion flux dependent and independent functions of various cardiac ion channels.

Figure 1

Stages of heart development in zebrafish embryos in a ventral view. (a) At 15 hpf cardiac precursors move towards the anterior lateral plate mesoderm; the atrial precursors are located laterally, the ventricular precursors medially. (b) Cardiac fusion starts at about 18 hpf at the posterior end of the bilateral heart fields; first, endocardial cells arrive at midline, followed by ventricular cells. The atrial precursors do so slightly later. (c) After cardiac fusion the cells form the cardiac cone. Viewed ventrally, this structure resembles a ring: endocardial cells lining the central lumen, and ventricular cells are surrounded by atrial precursors. The cardiac cone starts to transform into the heart tube by 21 hpf. (d) Cardiac looping of the heart tube occurs between 26 hpf and 48 hpf. The linear heart tube bends and creates an S-shaped loop. By 36 hpf the atrium and ventricle become distinguishable. (e) The heart tube rotates. The different parts of the heart tube do not rotate equally and therefore torsion occurs. The AV canal develops by constriction of the boundary between atrium and ventricle. Ventricular maturation by appositional growth takes place.