Clinical & Experimental Cardiology
Open Access
ISSN: 2155-9880
+44 1300 500008
ISSN: 2155-9880
+44 1300 500008
Susmita Chakrabarti, Miroslava Tischenko, Qiuyun Chen and Qing K Wang
Cleveland Clinic, USA
Posters & Accepted Abstracts: J Clin Exp Cardiolog
Despite tremendous improvements in its prevention and treatment, cardiac-arrhythmias are the major cause of morbidity and mortality worldwide accounting for >1.2 million hospitalizations and 400,000 sudden-deaths each year in the United States. The cardiac voltage gated sodium channel, Nav1.5, is crucial for maintaining normal cardiac rhythm. Loss-of-function mutations in the Nav1.5-encoding gene SCN5A cause a vast array of cardiac disorders including Brugada syndrome (BrS), sick sinus syndrome (SSS), dilated cardiomyopathy (DCM), cardiac conduction disease (CCD) and atrial fibrillation (AF). However, no effective treatment is available for these syndromes, except for invasive implantation of defibrillators or pacemakers in some cases. Defects in cellsurface- trafficking of ion-channels have been demonstrated to be a unique molecular mechanism underlying a variety of arrhythmic disorders. As SCN5A-mutations causing BrS, DCM and SSS act by loss-of-function; agents increasing cardiac-sodium-current (INa) may aid towards safe, effective treatment. In 2008, we reported that a 20 kD protein MOG1 is a novel cofactor modulating Nav1.5- function. In 2013, we demonstrated the therapeutic potential of MOG1 in vitro to rescue the Nav1.5-trafficking-defects and reduced INa associated with BrS, DCM and SSS. We are currently evaluating the therapeutic potential of MOG1 in vivo. Reduced INa has also been associated with inherited cardiovascular disorders like myocardial infarctions/ ischemia and heart-failure. Thus, the MOG1- therapy to facilitate membrane-trafficking of Nav1.5 may be utilized for the trafficking-defective subset of cardiac channelopathies.
Email: chakras3@ccf.org