title: Diabetes decreases mRNA levels of calcium-release channels in human atrial appendage.
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).
authors: Department of Pharmacology, Faculty of Pharmacy, University of Ankara, Tandogan 06100, Ankara, Turkey.
authors: Sahika
authors: S
authors: Guner
authors: Department of Pharmacology, Faculty of Pharmacy, University of Ankara, Tandogan 06100, Ankara, Turkey.
authors: Ebru
authors: E
authors: Arioglu
authors: Department of Pharmacology, Faculty of Pharmacy, University of Ankara, Tandogan 06100, Ankara, Turkey.
authors: Aydin
authors: A
authors: Tay
authors: Department of Pharmacology, Faculty of Pharmacy, University of Ankara, Tandogan 06100, Ankara, Turkey.
authors: Atalay
authors: A
authors: Tasdelen
authors: Department of Pharmacology, Faculty of Pharmacy, University of Ankara, Tandogan 06100, Ankara, Turkey.
authors: Sait
authors: S
authors: Aslamaci
authors: Department of Pharmacology, Faculty of Pharmacy, University of Ankara, Tandogan 06100, Ankara, Turkey.
authors: Keshore R
authors: KR
authors: Bidasee
authors: Department of Pharmacology, Faculty of Pharmacy, University of Ankara, Tandogan 06100, Ankara, Turkey.
authors: U Deniz
authors: UD
authors: Dincer
keywords: 1,4,5-trisphosphate receptors; calcium-release channels; diabetes; expression; human atrial appendage; inositol; reverse transcription-polymerase chain reaction; ryanodine receptors