Diabetes decreases mRNA levels of calcium-release channels in human atrial appendage.
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 (IP(3)Rs)) 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 IP(3)Rs. 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 IP(3)Rs in human atrial appendage. IP(3)R1 decreased by 24.2 +/- 4.6%, IP(3)R2 decreased by 63.0 +/- 4.6% and IP(3)R3 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.
Guner
Sahika
S
Department of Pharmacology, Faculty of Pharmacy, University of Ankara, Tandogan 06100 Ankara, Turkey.
Arioglu
Ebru
E
Tay
Aydin
A
Tasdelen
Atalay
A
Aslamaci
Sait
S
Bidasee
Keshore R
KR
Dincer
U Deniz
UD
D000368:Aged; D001483:Base Sequence; D015220:Calcium Channels / Q000235:genetics*; D016022:Case-Control Studies; D001026:Coronary Artery Bypass; D018076:DNA, Complementary / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D006325:Heart Atria / Q000378:metabolism; D006339:Heart Rate; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
D015220:Calcium Channels; D018076:DNA, Complementary; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel