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Diabetes decreases mRNA levels of calcium-release channels in human atrial appendage

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Abstract

Patients with chronic diabetes mellitus usually develop reductions in rate and force of cardiac contractions. Since calcium-release channels (ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs)) play integral roles in effecting these processes, we rationalize that alterations in their expression may underlie these defects. To test this hypothesis, right atrial appendages were obtained from diabetic (65.0 ± 4.5 years) and nondiabetic (56.2 ± 2.6 years) patients undergoing coronary arterial by-pass grafting and reverse transcription-polymerase chain reactions were used to compare steady state levels of mRNA encoding the three major isoforms of RyRs and IP3Rs. In this study we did not detect either RyR1 or RyR3 in human atrial appendage. When compared with nondiabetic patients, mRNA encoding RyR2 from diabetic patients decreased by 74.2 ± 6.2% (p< 0.01). Diabetes also significantly decreased steady-state levels of mRNA encoding the IP3Rs in human atrial appendage. IP3R1 decreased by 24.2 ± 4.6%, IP3R2 decreased by 63.0 ± 4.6% and IP3R3 decreased by 55.5 ± 6.5%. Since a reduction in steady-state mRNA is usually indicative of a decrease in protein levels, these data suggest that the decrease in chronotropy and inotropy seen in chronic diabetic patients may be due in part to a decrease in expression of calcium-release channels. (Mol Cell Biochem 263: 143–150, 2004)

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmacy, University of Ankara, Tandogan 06100, Ankara, Turkey

    Sahika Guner, Ebru Arioglu, Aydin Tay, Atalay Tasdelen, Sait Aslamaci, Keshore R. Bidasee & U. Deniz Dincer

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  1. Sahika Guner
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  2. Ebru Arioglu
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  3. Aydin Tay
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Guner, S., Arioglu, E., Tay, A. et al. Diabetes decreases mRNA levels of calcium-release channels in human atrial appendage. Mol Cell Biochem 263, 143–150 (2004). https://doi.org/10.1023/B:MCBI.0000041856.92497.0c

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