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Effects of streptozotocin-induced diabetes on connexin43 mRNA and protein expression in ventricular muscle

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Abstract

Abnormal QT prolongation with the associated arrhythmias is a significant predictor of mortality in diabetic patients. Gap junctional intercellular communication allows electrical coupling between heart muscle cells. The effects of streptozotocin (STZ)-induced diabetes mellitus on the expression and distribution of connexin 43 (Cx43) in ventricular muscle have been investigated. Cx43 mRNA expression was measured in ventricular muscle by quantitative PCR. The distribution of total Cx43, phosphorylated Cx43 (at serine 368) and non-phosphorylated Cx43 was measured in ventricular myocytes and ventricular muscle by immunocytochemistry and confocal microscopy. There was no significant difference in Cx43 mRNA between diabetic rat ventricle and controls. Total and phosphorylated Cx43 were significantly increased in ventricular myocytes and ventricular muscle and dephosphorylated Cx43 was not significantly altered in ventricular muscle from diabetic rat hearts compared to controls. Disturbances in gap junctional intercellular communication, which in turn may be attributed to alterations in balance between total, phosphorylated and dephosporylated Cx43, might partly underlie prolongation of QRS and QT intervals in diabetic heart.

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Acknowledgements

This work was supported by grants from the United Arab Emirates University (01-05-8-11/07) and the British Heart Foundation, and a travel bursary from the British Council, Abu Dhabi, UAE. Ms Natalie J. Chandler was supported by the Welcome Trust (vacation scholarship award no. VS/04/LEE/A2/OA/AM/FH).

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates

    F. C. Howarth

  2. Cardiovascular Research Group, University of Manchester, Manchester, UK

    N. J. Chandler, J. O. Tellez, I. D. Greener, M. R. Boyett & H. Dobrzynski

  3. Biological Physics Group, School of Physics & Astronomy, University of Manchester, Manchester, UK

    S. Kharche & H. Zhang

  4. Kagawa Prefectural College of Health Sciences, Kagawa, Japan

    T. T. Yamanushi

  5. School of Biomedical Sciences, University of Nottingham, Nottingham, UK

    R. Billeter

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  1. F. C. Howarth
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Correspondence to F. C. Howarth.

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The authors F.C. Howarth, N.J. Chandler contributed equally to this work.

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Howarth, F.C., Chandler, N.J., Kharche, S. et al. Effects of streptozotocin-induced diabetes on connexin43 mRNA and protein expression in ventricular muscle. Mol Cell Biochem 319, 105–114 (2008). https://doi.org/10.1007/s11010-008-9883-5

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  • DOI: https://doi.org/10.1007/s11010-008-9883-5

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