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Altered expression of gap junction connexin proteins may partly underlie heart rhythm disturbances in the streptozotocin-induced diabetic rat heart

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Abstract

Previous studies in isolated perfused heart and in atrial preparations have demonstrated significant reductions in beating rate in STZ-induced diabetic rats, which suggests that sinus arrhythmias in diabetes mellitus may be partly caused by intrinsic alteration of sino-atrial node (SAN) function. The effects of diabetes on electrical activity and expression levels of mRNA for gap junction proteins in the SAN have been investigated. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) administered to young male Wistar rats (200–250 g). Experiments were performed 8–10 weeks after treatment. Conduction time and pacemaker cycle length were measured in sino-atrial node preparations with extracellular electrodes. Expression levels of mRNA for Gja5 (C×40), Gja1 (C×43) and Gja7 (C×45) were measured in SAN and compared with right atrium and right ventricle with real-time quantitative reverse transcription-polymerase chain reaction. Diabetes was confirmed by a significant elevation of blood glucose (356 ± 21 mg/dl) compared to age-matched controls (66 ± 2 mg/dl). Pacemaker cycle length was significantly prolonged in diabetic heart (415 ± 43 ms, n = 6) compared to controls (255 ± 7 ms, n = 6). Sino-atrial conduction time was also significantly prolonged in diabetic hearts (12 ± 2 ms) compared to controls (7 ± 1 ms). Expression levels of mRNA for Gja5 (C×40) and Gja1 (C×43) were moderately increased and for Gja7 (C×45) was significantly increased in SAN from diabetic heart compared to controls. Expression levels for gap junction connexin proteins were not significantly altered in right atrium or right ventricle from diabetic heart compared to controls. Structural remodelling of gap junction connexin proteins may partly underlie electrophysiological defects in STZ-induced diabetic rat SAN.

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Acknowledgements

This work was funded by grants from the UAE University (Chris Howarth), Welcome Trust (Ming Lei) and by a travel bursary from the British Council (Chris Howarth), Abu Dhabi, UAE.

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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, UAE

    F. C. Howarth

  2. Zoonoses and Emerging Infections Group, Clinical Virology, Clinical Department of Diagnostic Imaging, Infections Diseases and Clinical Pathology, University of Veterinary Medicine, Vienna Veterinaerplatz 1, A-1210, Vienna, Austria

    N. Nowotny

  3. Department of Medical Microbiology, Faculty of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE

    E. Zilahi & M. A. El Haj

  4. Division of Cardiovascular Sciences, School of Medicine, University of Manchester, Manchester, UK

    M. Lei

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

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Howarth, F.C., Nowotny, N., Zilahi, E. et al. Altered expression of gap junction connexin proteins may partly underlie heart rhythm disturbances in the streptozotocin-induced diabetic rat heart. Mol Cell Biochem 305, 145–151 (2007). https://doi.org/10.1007/s11010-007-9537-z

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