Abstract
Abstract 503: Nicotinamide Riboside Modulates Late Sodium Current and Cardiac Repolarization
Circulation research, Vol.125(Suppl_1)
08/02/2019
DOI: 10.1161/res.125.suppl_1.503
Abstract
Background:
Boosting NAD
+
content within the heart has emerged as a cardioprotective strategy against heart failure-related remodeling, ischemic injury, and arrhythmias. Our group recently demonstrated that the bioavailable NAD
+
precursor Nicotinamide Riboside (NR) drives Sirtuin 1-mediated deacetylation of the main cardiac sodium channel Na
v
1.5 to increase peak sodium current (I
Na
), a major determinant of cardiac excitability and action potential conduction. However, the effects of NAD
+
precursors and NR on cardiac repolarization are relatively unexplored.
Objective:
To evaluate the effects of NR on late Na
+
current and cardiac repolarization.
Methods:
To study the
in vitro
effects of NR, whole-cell patch clamp was utilized to measure I
Na
and late sodium current (I
NaL
) in myocytes isolated from 1-3 day old neonatal rats (NRCMs). To study the
in vivo
effects of NR, 4-5 month-old C57BL/6 mice were placed on either a control diet or a diet supplemented with NR (1%). EKGs were performed at baseline, 6 weeks, and 12 weeks post-diet.
Results:
NR increased peak I
Na
(500 uM: +60.1 ± 26%, 5 mM: +74.7 ± 39%) with a non-significant change in absolute I
NaL
(500 uM: -12.8 ± 9%, 5 mM: -32.4 ± 20%)
,
leading to decreased I
NaL
when normalized to peak current (500 uM: -45.2 ± 7.8%, 5 mM: -51.6 ± 9.8%, Figure A,B). Additionally, 12-week dietary NR supplementation shortened QT
c
in NR-treated mice (-9.1 ± 4.6%) but not in control mice (+1.7 ± 1.3%, Figure C).
Conclusion:
NAD
+
supplementation with NR is potentially anti-arrhythmic by decreasing I
NaL
and shortening QT
c
. Potential mechanisms include mitigating the effects of oxidative stress and/or modulation of PKA and PKC phosphorylation of Na
v
1.5.
Details
- Title: Subtitle
- Abstract 503: Nicotinamide Riboside Modulates Late Sodium Current and Cardiac Repolarization
- Creators
- Daniel S Matasic - University of IowaPravda Quinones - University of IowaCharles Brenner - University of IowaBarry London - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Circulation research, Vol.125(Suppl_1)
- DOI
- 10.1161/res.125.suppl_1.503
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 08/02/2019
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984302190502771
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