Cardiac voltage-gated sodium channel expression and electrophysiological characterization of the sodium current in the zebrafish (Danio rerio) ventricle.

Na+ channel α-subunit composition of the zebrafish heart and electrophysiological properties of Na+ current (INa) of zebrafish ventricular myocytes were examined. Eight Na+ channel α-subunits were expressed in both atrium and ventricle of the zebrafish heart. Nav1.5Lb, an orthologue to the human Nav1.5, was clearly the predominant isoform in both chambers representing 65.2 ± 4.1% and 83.1 ± 2.1% of all Na+ channel transcripts in atrium and ventricle, respectively. Nav1.4b, an orthologue to human Nav1.4, formed 34.1 ± 4.1 and 16.2 ± 2.0% of the Na+ channel transcripts in atrium and ventricle, respectively. The density of INa and the rate of action potential upstroke in zebrafish ventricular myocytes at 28 °C were similar to those of human ventricles at the comparable temperature. Na+ channel isoforms and the main electrophysiological characteristics of the INa are largely similar in zebrafish and human hearts indicating evolutionary conservation of Na+ channel composition and function. The zebrafish INa differs from the human cardiac INa in terms of higher tetrodotoxin sensitivity (IC50-value = 5.3 ± 0.1 nM) and slower inactivation kinetics. The zebrafish INa was inhibited with tricaine (MS-222) with an IC50-value of 1.2 ± 0.18 mM (336 mg l-1), suggesting some care in the use of MS-222 as an anesthetic.