Enhanced SERCA2A expression improves contractile performance of ventricular cardiomyocytes of rat under adrenergic stimulation.
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.
Anwar
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A
Institute of Physiology, Justus-Liebig-University, Aulweg 129, 35392, Giessen, Germany.
Schlüter
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KD
Heger
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Piper
H M
HM
Euler
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G
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004790:Enzyme Induction; D006339:Heart Rate; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology; D050778:NFATC Transcription Factors / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; C506948:Atp2a2 protein, rat; D002316:Cardiotonic Agents; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine