Obstetric cholestasis is characterized by raised bile acids, and can be complicated by intrauterine death. We have shown that the bile acid taurocholate causes loss of synchronous beating, bradycardia and cessation of contraction in cultured rat cardiomyocytes [Williamson, Gorelik, Eaton, Lab, de Swiet and Korchev (2001) Clin. Sci. 100, 363–369]. The aim of the present study was to investigate the effect of taurocholate on cardiomyocytes further. We demonstrated a reduced rate of contraction and proportion of beating cells when rat cardiomyocytes were exposed to increasing concentrations of taurocholate (0.1–3.0mM); more marked at higher concentrations (P<0.001). Using scanning ion-conductance microscopy, we also demonstrated reduced amplitude of contraction and calcium transients with taurocholate. Our observations indicate that taurocholate affects calcium release from the sarcoplasmic reticulum and this parallels changes in contractile function. The relationship between the contraction amplitude and calcium transient is not linear, particularly at higher concentrations of taurocholate. We observed different effects in individual cultured neonatal cells; a reversible reduction in rate and amplitude of contraction in some, and irreversible oscillatory (fibrillatory) cessation of beating in others. The effects were more marked with higher concentrations. The contraction amplitude was also reduced in adult cardiomyocytes. The changes were reversible following removal of taurocholate in adult, but not in neonatal, cardiomyocytes exposed to higher concentrations (>0.3mM) (P<0.001). In conclusion we have demonstrated that the bile acid taurocholate can cause different types of dysrhythmia in individual cardiomyocytes. These results provide further support for the hypothesis that obstetric cholestasis may produce cardiac-related sudden intrauterine death.
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Research Article|
July 17 2002
Taurocholate induces changes in rat cardiomyocyte contraction and calcium dynamics
Julia GORELIK;
Julia GORELIK
*Division of Medicine, Imperial College School of Medicine, MRC Clinical Sciences Centre, Hammersmith Campus, Du Cane Road, London W12 0NN, U.K.
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Sian E. HARDING;
Sian E. HARDING
†National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St, London SW3 6LY, U.K.
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Andrew I. SHEVCHUK;
Andrew I. SHEVCHUK
*Division of Medicine, Imperial College School of Medicine, MRC Clinical Sciences Centre, Hammersmith Campus, Du Cane Road, London W12 0NN, U.K.
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Duleepa KORALAGE;
Duleepa KORALAGE
*Division of Medicine, Imperial College School of Medicine, MRC Clinical Sciences Centre, Hammersmith Campus, Du Cane Road, London W12 0NN, U.K.
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Max LAB;
Max LAB
‡National Heart and Lung Institute, Imperial College School of Medicine, Charing Cross Campus, Fulham Palace Road, London W6 8RF, U.K.
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Michael DE SWIET;
Michael DE SWIET
§Division of Paediatrics, Obstetrics and Gynaecology, Imperial College School of Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, U.K.
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Yuri KORCHEV;
Yuri KORCHEV
*Division of Medicine, Imperial College School of Medicine, MRC Clinical Sciences Centre, Hammersmith Campus, Du Cane Road, London W12 0NN, U.K.
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Catherine WILLIAMSON
*Division of Medicine, Imperial College School of Medicine, MRC Clinical Sciences Centre, Hammersmith Campus, Du Cane Road, London W12 0NN, U.K.
§Division of Paediatrics, Obstetrics and Gynaecology, Imperial College School of Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, U.K.
Correspondence: Dr C. Williamson, ICSTM Maternal and Fetal Disease Group, Institute of Reproductive and Developmental Biology, Hammersmith Hospital, Du Cane Road, London W12 0NN, U.K. (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
November 27 2001
Revision Received:
March 14 2002
Accepted:
May 01 2002
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2002
2002
Clin Sci (Lond) (2002) 103 (2): 191–200.
Article history
Received:
November 27 2001
Revision Received:
March 14 2002
Accepted:
May 01 2002
Citation
Julia GORELIK, Sian E. HARDING, Andrew I. SHEVCHUK, Duleepa KORALAGE, Max LAB, Michael DE SWIET, Yuri KORCHEV, Catherine WILLIAMSON; Taurocholate induces changes in rat cardiomyocyte contraction and calcium dynamics. Clin Sci (Lond) 1 August 2002; 103 (2): 191–200. doi: https://doi.org/10.1042/cs1030191
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