Cardiac Na+ Current Regulation by Pyridine Nucleotides

RATIONALE:Mutations in glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) protein reduce cardiac Na current (INa) and cause Brugada Syndrome (BrS). GPD1-L has >80% amino acid homology with glycerol-3-phosphate dehydrogenase, which is involved in NAD-dependent energy metabolism. OBJECTIVE:Therefor...

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Veröffentlicht in:	Circulation research 2009-10, Vol.105 (8), p.737-745
Hauptverfasser:	Liu, Man, Sanyal, Shamarendra, Gao, Ge, Gurung, Iman S, Zhu, Xiaodong, Gaconnet, Georgia, Kerchner, Laurie J, Shang, Lijuan L, Huang, Christopher L.-H, Grace, Andrew, London, Barry, Dudley, Samuel C
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antineoplastic Agents - pharmacology Benzophenanthridines - pharmacology Biological and medical sciences Brugada Syndrome - genetics Brugada Syndrome - metabolism Cardiac dysrhythmias Cardiology. Vascular system Cell Line Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors Cyclic AMP-Dependent Protein Kinases - genetics Cyclic AMP-Dependent Protein Kinases - metabolism Down-Regulation - drug effects Down-Regulation - genetics Enzyme Inhibitors - pharmacology Fundamental and applied biological sciences. Psychology Glycerolphosphate Dehydrogenase - genetics Glycerolphosphate Dehydrogenase - metabolism Heart Humans Medical sciences Mice Muscle Proteins - genetics Muscle Proteins - metabolism Mutation Myocardium - metabolism NAD - genetics NAD - metabolism NAV1.5 Voltage-Gated Sodium Channel Oxidation-Reduction Protein Kinase C - antagonists & inhibitors Protein Kinase C - genetics Protein Kinase C - metabolism Rats Sodium - metabolism Sodium Channels - genetics Sodium Channels - metabolism Superoxide Dismutase - genetics Superoxide Dismutase - metabolism Tachycardia, Ventricular - genetics Tachycardia, Ventricular - metabolism Vertebrates: cardiovascular system
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Zusammenfassung:	RATIONALE:Mutations in glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) protein reduce cardiac Na current (INa) and cause Brugada Syndrome (BrS). GPD1-L has >80% amino acid homology with glycerol-3-phosphate dehydrogenase, which is involved in NAD-dependent energy metabolism. OBJECTIVE:Therefore, we tested whether NAD(H) could regulate human cardiac sodium channels (Nav1.5). METHODS AND RESULTS:HEK293 cells stably expressing Nav1.5 and rat neonatal cardiomyocytes were used. The influence of NADH/NAD on arrhythmic risk was evaluated in wild-type or SCN5A mouse heart. A280V GPD1-L caused a 2.48±0.17-fold increase in intracellular NADH level (P
ISSN:	0009-7330 1524-4571
DOI:	10.1161/CIRCRESAHA.109.197277