ArticleJournal of cellular biochemistry2008
Increased intracellular [dATP] enhances cardiac contraction in embryonic chick cardiomyocytes.
Article in Journal of cellular biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- A sensitive assay for dNTPs based on long synthetic oligonucleotides, EvaGreen dye and inhibitor-resistant high-fidelity DNA polymerase.Nucleic acids research · 2020Article
- Cardiac Myosin Activation with Gene Therapy Produces Sustained Inotropic Effects and May Treat Heart Failure with Reduced Ejection Fraction.Handbook of experimental pharmacology · 2017Review
- Translation of Cardiac Myosin Activation with 2-deoxy-ATP to Treat Heart Failure via an Experimental Ribonucleotide Reductase-Based Gene Therapy.JACC. Basic to translational science · 2016Article
- Cell-based delivery of dATP via gap junctions enhances cardiac contractility.Journal of molecular and cellular cardiology · 2014Article
- Nuclear tropomyosin and troponin in striated muscle: new roles in a new locale?Journal of muscle research and cell motility · 2013Review
- Transgenic overexpression of ribonucleotide reductase improves cardiac performance.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Upregulation of cardiomyocyte ribonucleotide reductase increases intracellular 2 deoxy-ATP, contractility, and relaxation.Journal of molecular and cellular cardiology · 2011Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Although ATP is the physiological substrate for cardiac contraction, cardiac contractility is significantly enhanced in vitro when only 10% of ATP substrate is replaced with 2'-deoxy-ATP (dATP). To determine the functional effects of increased intracellular [dATP] ([dATP](i)) within living cardiac cells, we used hypertonic loading with varying exogenous dATP/ATP ratios, but constant total nucleotide concentration, to elevate [dATP](i) in contractile monolayers of embryonic chick cardiomyocytes. The increase in [dATP](i) was estimated from dilution of dye added in parallel with dATP. Cell viability, average contractile amplitude, rates of contraction/relaxation, spontaneous beat frequency, and Ca2+ transient amplitude and kinetics were examined. At total [dATP](i) above approximately 70 microM, spontaneous contractions ceased, and above approximately 100 microM [dATP](i), membrane blebbing was also observed, consistent with apoptosis. Interestingly, [dATP](i) of approximately 60 microM ( approximately 40% increase over basal [dATP](i) levels) enhanced both amplitude of contraction and the rates of contraction and relaxation without affecting beat frequency. With total [dATP](i) of approximately 60 microM or less, we found no significant change in Ca2+ transients. These data indicate that there is an "optimal" concentration of exogenously loaded [dATP](i) that under controlled conditions can enhance contractility in living cardiomyocytes without affecting beat frequency or Ca2+ transients.
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Registered trials
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