Bacterial toxins and heart function: heat-labile Escherichia coli enterotoxin B promotes changes in cardiac function with possible relevance for sudden cardiac death

Bacterial toxins can cause cardiomyopathy, though it is not its most common cause. Some bacterial toxins can form pores in the membrane of cardiomyocytes, while others can bind to membrane receptors. Enterotoxigenic E. coli can secrete enterotoxins, including heat-resistant (ST) or labile (LT) enterotoxins. LT is an AB 5 -type toxin that can bind to specific cell receptors and disrupt essential host functions, causing several common conditions, such as certain diarrhea. The pentameric B subunit of LT, without A subunit (LTB), binds specifically to certain plasma membrane ganglioside receptors, found in lipid rafts of cardiomyocytes. Isolated guinea pig hearts and cardiomyocytes were exposed to different concentrations of purified LTB. In isolated hearts, mechanical and electrical alternans and an increment of heart rate variability, with an IC50 of ~0.2 μg/ml LTB, were observed. In isolated cardiomyocytes, LTB promoted significant decreases in the amplitude and the duration of action potentials. Na + currents were inhibited whereas L-type Ca 2+ currents were augmented at their peak and their fast inactivation was promoted. Delayed rectifier K + currents decreased. Measurements of basal Ca 2+ or Ca 2+ release events in cells exposed to LTB suggest that LTB impairs Ca 2+ homeostasis. Impaired calcium homeostasis is linked to sudden cardiac death. The results are consistent with the recent view that the B subunit is not merely a carrier of the A subunit, having a role explaining sudden cardiac death in children (SIDS) infected with enterotoxigenic E. coli , explaining several epidemiological findings that establish a strong relationship between SIDS and ETEC E. coli .