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

Simona Esposito Lauren R McGuinness Parveen Sharma Amy E Chadwick Richard Daniel Rainbow ^*

• University of Liverpool, Liverpool, United Kingdom

Trimethylamine 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 a role for TMAO as either a marker or causative of disease. These investigations examined whether TMAO had an effect on cardiomyocyte contractile function, calcium homeostasis and survival from metabolic insult.TMAO had no effect on metabolic function or the ability of cells to survive a metabolic insult, however 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 were not observed following 24 hour 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.These data suggest that high TMAO concentrations in the blood of patients may be a marker of potential cardiovascular disease rather than having a causative role.