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 (I_Na) of zebrafish ventricular myocytes were examined. Eight Na⁺ channel α-subunits were expressed in both atrium and ventricle of the zebrafish heart. Na_v1.5Lb, an orthologue to the human Na_v1.5, 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. Na_v1.4b, an orthologue to human Na_v1.4, formed 34.1 ± 4.1 and 16.2 ± 2.0% of the Na⁺ channel transcripts in atrium and ventricle, respectively. The density of I_Na 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 I_Na are largely similar in zebrafish and human hearts indicating evolutionary conservation of Na⁺ channel composition and function. The zebrafish I_Na differs from the human cardiac I_Na in terms of higher tetrodotoxin sensitivity (IC₅₀-value = 5.3 ± 0.1 nM) and slower inactivation kinetics. The zebrafish I_Na 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.

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