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Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique
Published on: November 11, 2022
Cardiac Na+ current regulation by pyridine nucleotides
Man Liu1, Shamarendra Sanyal, Ge Gao
1Division in Cardiology, University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Chicago, IL 60612, USA.
Circulation Research
|September 12, 2009
Summary
Mutations in GPD1-L protein, linked to Brugada Syndrome, alter cellular metabolism. This study reveals that NAD(H) regulates cardiac sodium channels (Na(v)1.5), impacting arrhythmic risk.
Area of Science:
- Cardiology
- Molecular Biology
- Metabolic Regulation
Background:
- Mutations in glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) protein are associated with Brugada Syndrome (BrS) by reducing cardiac sodium current (I(Na)).
- GPD1-L shares homology with glycerol-3-phosphate dehydrogenase, an enzyme critical for NAD-dependent energy metabolism.
Purpose of the Study:
- To investigate whether NAD(H) levels directly regulate human cardiac sodium channels (Na(v)1.5).
- To explore the link between cellular metabolism and cardiac electrophysiology.
Main Methods:
- Utilized HEK293 cells expressing Na(v)1.5 and rat neonatal cardiomyocytes.
- Assessed the impact of altered intracellular NADH levels (induced by A280V GPD1-L mutation) on I(Na).
- Evaluated the influence of NAD(H) on arrhythmic risk in wild-type and SCN5A(+/-) mouse hearts.
Main Results:
- Increased intracellular NADH levels, caused by A280V GPD1-L, significantly decreased I(Na).
- NAD+ reversed the NADH-induced I(Na) reduction, an effect mediated by protein kinase C (PKC) activation and oxidative stress.
- NADH application increased ventricular tachycardia risk in mouse hearts, while extracellular NAD+ ameliorated this risk in SCN5A(+/-) hearts.
Conclusions:
- Cardiac Na(v)1.5 channels are regulated by pyridine nucleotides (NAD(H)), establishing a connection between cellular metabolism and cardiac sodium current.
- GPD1-L mutations may lead to Na(v)1.5 downregulation by disrupting the NAD(H) balance.
- NAD+ administration shows potential in mitigating arrhythmogenic risks associated with metabolic dysregulation.
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