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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
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Published on: July 3, 2013

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

Sahika Guner1, Ebru Arioglu, Aydin Tay

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

Molecular and Cellular Biochemistry
|November 5, 2004
PubMed

Insights

Diabetic patients show reduced heart contraction rates and forces. This study found decreased expression of calcium-release channels, specifically RyR2 and IP3Rs, in diabetic hearts, potentially explaining these cardiac defects.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Biology
  • Endocrinology

Background:

  • Chronic diabetes mellitus is associated with impaired cardiac contractility (reduced rate and force).
  • Calcium-release channels, including ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs), are critical for cardiac contraction.
  • Alterations in the expression of these channels may contribute to diabetic cardiomyopathy.

Purpose of the Study:

  • To investigate the hypothesis that altered expression of RyRs and IP3Rs underlies cardiac dysfunction in chronic diabetes mellitus.
  • To compare the mRNA expression levels of RyR and IP3R isoforms in atrial appendages from diabetic and non-diabetic patients.

Main Methods:

  • Right atrial appendages were obtained from diabetic and non-diabetic patients undergoing coronary artery bypass grafting.
  • Reverse transcription-polymerase chain reaction (RT-PCR) was employed to quantify steady-state mRNA levels of RyR and IP3R isoforms.

Main Results:

  • RyR1 and RyR3 mRNA were not detected in human atrial appendages.
  • Diabetic patients exhibited a significant decrease in RyR2 mRNA expression (74.2% reduction) compared to non-diabetic controls.
  • Significant reductions in IP3R1 (24.2%), IP3R2 (63.0%), and IP3R3 (55.5%) mRNA levels were observed in diabetic patients.

Conclusions:

  • The findings suggest that decreased expression of RyR2 and IP3Rs in the heart contributes to the impaired cardiac contractility observed in chronic diabetes mellitus.
  • Reduced steady-state mRNA levels likely indicate a corresponding decrease in protein expression, impacting calcium handling and cardiac function.

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