Atrium-specific ion channels in the zebrafish-A role of I_KACh in atrial repolarization

The zebrafish has emerged as a novel model for investigating cardiac physiology and pathology. The aim of this study was to investigate the atrium-specific ion channels responsible for shaping the atrial cardiac action potential in zebrafish.

Using quantitative polymerase chain reaction, we assessed the expression level of atrium-specific potassium channels. The functional role of these channels was studied by patch clamp experiments on isolated atrial and ventricular cardiomyocytes and by optical mapping of explanted adult zebrafish hearts. Finally, surface ECGs were recorded to establish possible in vivo roles of atrial ion channels.

In isolated adult zebrafish hearts, we identified the expression of kcnk3, kcnk9, kcnn1, kcnn2, kcnn3, kcnj3 and kcnj5, the genes that encode the atrium-specific K_2P , K_Ca 2.x and K_ir 3.1/4 (K_ACh ) ion channels. The electrophysiological data indicate that the acetylcholine-activated inward-rectifying current, I_KACh, plays a major role in the zebrafish atrium, whereas K_2P 3.1/9.1 and K_Ca 2.x channels do not appear to be involved in regulating the action potential in the zebrafish heart.

We demonstrate that the acetylcholine-activated inward-rectifying current (I_KACh ) current plays a major role in the zebrafish atrium and that the zebrafish could potentially be a cost-effective and reliable model for pharmacological testing of atrium-specific I_KACh modulating compounds.