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

Autor: Klaus-Dieter Schlüter, Attia Anwar, Gerhild Euler, Jacqueline Heger, H. M. Piper
Rok vydání: 2008
Předmět:
Zdroj: Pflügers Archiv - European Journal of Physiology. 457:485-491
ISSN: 1432-2013
0031-6768
DOI: 10.1007/s00424-008-0520-7
Popis: 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.
Databáze: OpenAIRE
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