PubMed 20339120

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Nav1.5

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

Authors: Sameer S Chopra, Dina Myers Stroud, Hiroshi Watanabe, Jeffrey S Bennett, C Geoffrey Burns, K Sam Wells, Tao Yang, Tao P Zhong, Dan M Roden

Journal, date & volume: Circ. Res., 2010 Apr 30 , 106, 1342-50

PubMed link:

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.Here we addressed this question by investigating the role of cardiac sodium channels in zebrafish heart development.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.These findings identify a novel and possibly nonelectrogenic role for cardiac sodium channels in heart development.