Dan Roden
Faculty Member
Last active: 2/8/2016

Voltage-gated sodium channels are required for heart development in zebrafish.

Chopra SS, Stroud DM, Watanabe H, Bennett JS, Burns CG, Wells KS, Yang T, Zhong TP, Roden DM
Circ Res. 2010 106 (8): 1342-50

PMID: 20339120 · PMCID: PMC2869449 · DOI:10.1161/CIRCRESAHA.109.213132

RATIONALE - Voltage-gated sodium channels initiate action potentials in excitable tissues. Mice in which Scn5A (the predominant sodium channel gene in heart) has been knocked out die early in development with cardiac malformations by mechanisms which have yet to be determined.

OBJECTIVE - Here we addressed this question by investigating the role of cardiac sodium channels in zebrafish heart development.

METHODS AND RESULTS - Transcripts of the functionally-conserved Scn5a homologs scn5Laa and scn5Lab were detected in the gastrulating zebrafish embryo and subsequently in the embryonic myocardium. Antisense knockdown of either channel resulted in marked cardiac chamber dysmorphogenesis and perturbed looping. These abnormalities were associated with decreased expression of the myocardial precursor genes nkx2.5, gata4, and hand2 in anterior lateral mesoderm and significant deficits in the production of cardiomyocyte progenitors. These early defects did not appear to result from altered membrane electrophysiology, as prolonged pharmacological blockade of sodium current failed to phenocopy channel knockdown. Moreover, embryos grown in calcium channel blocker-containing medium had hearts that did not beat but developed normally.

CONCLUSIONS - These findings identify a novel and possibly nonelectrogenic role for cardiac sodium channels in heart development.

MeSH Terms (30)

Age Factors Amino Acid Sequence Animals Animals, Genetically Modified Basic Helix-Loop-Helix Transcription Factors Cell Differentiation CHO Cells Cricetinae Cricetulus Gastrulation GATA Transcription Factors Gene Expression Regulation, Developmental Gene Knockdown Techniques Genotype Heart Heart Defects, Congenital Homeobox Protein Nkx-2.5 Membrane Potentials Molecular Sequence Data Morphogenesis Myocardium NAV1.5 Voltage-Gated Sodium Channel Oligonucleotides, Antisense Phenotype RNA, Messenger Sodium Channels Transcription Factors Transfection Zebrafish Zebrafish Proteins

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