Electrophysiological properties of cardiac myocytes in regenerating zebrafish hearts

Abstract

Zebrafish hearts fully regenerate within 30–60 days post‐amputation (dpa) of up to 20% of the ventricle. Lineage studies have shown regeneration is mediated by proliferation of existing myocytes. Genes encoding ion channel proteins undergo transcriptional changes during regeneration suggesting that electrical properties of the heart may be remodeled as part of the regenerative process. In these studies, we isolated myocytes from hearts 7 dpa, a time of peak myocyte proliferation, and characterized their electrical properties by patch clamp. Myocytes from uninjured and 30 dpa hearts had similar Na+, K+ and Ca2+ currents and action potentials. However, 7 dpa myocytes exhibited decreased T‐ and L‐type Ca2+ current amplitudes and a tendency to generate short duration action potentials. The T‐ and L‐type Ca2+ channel subunits CACNA1G, CACNA1C and CACN1B have reduced expression at 7 dpa. Our studies are the first to characterize ion channels in regenerating hearts. Reduced Ca2+ currents and shortened action potentials will reduce cardiac contractile forces, which may be required for regeneration. Changes in myocyte electrical activity and Ca2+ signaling may also play a role in regulating the regenerative process. Collectively, our studies document that dynamic changes in ion channel activity accompanies the transformation of quiescent myocytes into highly proliferative cardiac cells during regeneration.