Enhanced SERCA2A expression improves contractile performance of ventricular cardiomyocytes of rat under adrenergic stimulation.

Abstract

alpha-Adrenergic stimulation results in a positive adaptation of cardiomyocytes to increased cardiac work load by induction of hypertrophy and enhanced contraction. However, sustained adrenergic stimulation causes progression to heart failure. Under simultaneous activation of alpha- and beta-adrenoceptors by the naturally occurring catecholamine noradrenaline, beta1-stimulation inhibits alpha-adrenergic-stimulated hypertrophy. If beta-adrenergic stimulation may also influence cardiomyocyte contraction is not known yet. We now demonstrate that exposure of cardiomyocytes to noradrenaline or isoprenaline for 24 h results in a reduced cell shortening at low beating frequencies (0.5 Hz). At high beating frequencies (2 Hz), cell shortening was normal. beta-adrenergic stimulation enhances SERCA2A expression at the messenger RNA and protein level. This induction of the Ca(2+) pump SERCA2A by the transcription factor NFAT is responsible for maintenance of normal cell contraction at high beating frequencies since inhibition of NFAT by decoy-oligonucleotides impairs SERCA2A expression and cell shortening after beta-adrenergic stimulation. In conclusion, although reduced cell shortening is found under low beating frequencies, we demonstrate preservation of cardiomyocyte contraction at 2 Hz after exposure to beta-adrenergic stimuli, which indicate that adrenergic stimulation a priori does not cause impaired heart function. The increase of SERCA expression indicates an even improved Ca(2+) handling of the cells.

• Authors: A Anwar, K-D Schlüter, J Heger, H M Piper, G Euler
• Journal: Pflugers Archiv : European journal of physiology (Pflugers Arch) Vol. 457 Issue 2 Pg. 485-91 (Nov 2008) ISSN: 0031-6768 [Print] Germany
• PMID: 18581135 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Agonists
• Adrenergic beta-Agonists
• Atp2a2 protein, rat
• Cardiotonic Agents
• NFATC Transcription Factors
• RNA, Messenger
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• Isoproterenol
• Calcium
• Norepinephrine

Topics

• Adrenergic alpha-Agonists (pharmacology)
• Adrenergic beta-Agonists (pharmacology)
• Animals
• Calcium (metabolism)
• Cardiac Pacing, Artificial
• Cardiotonic Agents (pharmacology)
• Cells, Cultured
• Enzyme Induction
• Heart Rate
• Heart Ventricles (drug effects, enzymology)
• Isoproterenol (pharmacology)
• Male
• Myocardial Contraction (drug effects)
• Myocytes, Cardiac (drug effects, enzymology)
• NFATC Transcription Factors (metabolism)
• Norepinephrine (pharmacology)
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (biosynthesis, genetics)
• Time Factors