Trimethylamine N-oxide (TMAO) acutely alters ionic currents but does not increase cardiac cell death

Esposito, Simona, McGuinness, Lauren R, Sharma, Parveen ORCID: 0000-0002-5211-7177, Chadwick, Amy E ORCID: 0000-0002-7399-8655 and Rainbow, Richard D ORCID: 0000-0002-0532-1992 (2025) Trimethylamine N-oxide (TMAO) acutely alters ionic currents but does not increase cardiac cell death Frontiers in Physiology, 16. 1505813-. ISSN 1664-042X, 1664-042X

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Abstract

BackgroundTrimethylamine N-oxide (TMAO) is a product of the action of gut microbiota on choline and other choline-containing compounds ingested in the diet. The presence of TMAO at high concentrations has been reported in the blood of patients with cardiovascular disease, suggesting the role for TMAO as either a marker or causative agent of the disease. These investigations examined whether TMAO had an effect on cardiomyocyte contractile function, calcium homoeostasis, and survival from metabolic insult.ResultsTMAO had no effect on metabolic function or the ability of cells to survive a metabolic insult; however, it did cause transient changes to contractile function. These changes included an increase in calcium current and an increase in Kir6.1 channel activity in the cell, causing a shortening of the action potential duration to 90% repolarised but lengthening the action potential to 30% repolarised. These effects occurred within minutes of TMAO application; however, they were not observed following 24 h culture. These data suggest that TMAO does modulate contractile function, albeit only in the short-term, but has no effect on metabolic behaviour or the ability to withstand a metabolic challenge.ConclusionThese data suggest that high TMAO concentrations in the blood of patients may be a marker of potential cardiovascular disease rather than playing a causative role.

Item Type:	Article
Uncontrolled Keywords:	trimethylamine N-oxide, calcium channels, cardiac ATP-sensitive potassium channels, Kir6.1, biomarker
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	14 Feb 2025 08:18
Last Modified:	16 Jun 2026 20:05
DOI:	10.3389/fphys.2025.1505813
Open Access URL:	https://doi.org/10.3389/fphys.2025.1505813
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3190283
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