Comparison of the arrhythmogenic effects of tauro- and glycoconjugates of cholic acid in an in vitro study of rat cardiomyocytes.
Obstetric cholestasis is associated with intrauterine death. In obstetric cholestasis, primary bile acids are more commonly conjugated with taurine than glycine, while glycoconjugates predominate in normal pregnancy. Using an in vitro model of rat cardiomyocytes, we compared the effect of tauro- and glycoconjugated cholate on cardiomyocyte rhythm, contraction amplitude and network integrity. We demonstrated that taurocholate had a more marked effect on all of these parameters, and the effects of the glycoconjugates were fully reversible while those of tauroconjugates were not. The increased proportion of tauroconjugated bile acids in obstetric cholestasis may contribute to the aetiology of the intrauterine death associated with the condition.
Division of Medicine, Imperial College London, MRC Clinical Sciences Centre, Hammersmith Campus, UK.
J
J
Gorelik
A
A
Shevchuk
M
M
de Swiet
M
M
Lab
Y
Y
Korchev
C
C
Williamson
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002779:Cholestasis / Q000209:etiology; D019826:Cholic Acid / Q000009:adverse effects*; D005260:Female; D006001:Glycoconjugates / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000209:etiology; D051381:Rats; D013656:Taurocholic Acid / Q000494:pharmacology*
D006001:Glycoconjugates; D013656:Taurocholic Acid; D019826:Cholic Acid