MOG1 rescues defective trafficking of nav1.5 mutations in brugada syndrome and sick sinus syndrome

Susmita Chakrabarti, Xiaofen Wu, Zhaogang Yang, Ling Wu, Sandro L. Yong, Cuntai Zhang, Keli Hu, Qing K. Wang, Qiuyun Chen

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Background-Loss-of-function mutations in Nav1.5 cause sodium channelopathies, including Brugada syndrome, dilated cardiomyopathy, and sick sinus syndrome; however, no effective therapy exists. MOG1 increases plasma membrane (PM) expression of Nav1.5 and sodium current (I Na) density, thus we hypothesize that MOG1 can serve as a therapeutic target for sodium channelopathies. Methods and Results-Knockdown of MOG1 expression using small interfering RNAs reduced Nav1.5 PM expression, decreased INa densities by 2-fold in HEK/Nav1.5 cells and nearly abolished INa in mouse cardiomyocytes. MOG1 did not affect Nav1.5 PM turnover. MOG1 small interfering RNAs caused retention of Nav1.5 in endoplasmic reticulum, disrupted the distribution of Nav1.5 into caveolin-3-enriched microdomains, and led to redistribution of Nav1.5 to noncaveolin-rich domains. MOG1 fully rescued the reduced PM expression and INa densities by Na v1.5 trafficking-defective mutation D1275N associated with sick sinus syndrome/dilated cardiomyopathy/atrial arrhythmias. For Brugada syndrome mutation G1743R, MOG1 restored the impaired PM expression of the mutant protein and restored INa in a heterozygous state (mixture of wild type and mutant Nav1.5) to a full level of a homozygous wild-type state. Conclusions-Use of MOG1 to enhance Nav1.5 trafficking to PM may be a potential personalized therapeutic approach for some patients with Brugada syndrome, dilated cardiomyopathy, and sick sinus syndrome in the future.

Original languageEnglish (US)
Pages (from-to)392-401
Number of pages10
JournalCirculation: Arrhythmia and Electrophysiology
Issue number2
StatePublished - Apr 2013
Externally publishedYes


  • Cardiac sodium channel Na1.5
  • Cell surface expression
  • Ion channel trafficking
  • MOG1
  • SCN5A

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


Dive into the research topics of 'MOG1 rescues defective trafficking of nav1.5 mutations in brugada syndrome and sick sinus syndrome'. Together they form a unique fingerprint.

Cite this