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(Circulation. 2006;114:II_367-II_368.)
© 2006 American Heart Association, Inc.

Experimental and Clinical Insights into Ventricular Function

Abstract 1857: Improved Myocyte Contraction Via Upregulation Of SERCA Under Adrenergic Stimulation In Ventricular Cardiomyocytes Of Rat

Anwar Attia; K D Schluter; R Schreckenberg; H Korkusuz; T Berndt; Y Abdallah; M M Anwar; G Euler

Institute of Physiology, Giessen, Germany

Catecholamines contribute to the adaption of the heart to pressure overload via stimulation of adrenoceptors (- or ß-AR). While mechanisms resulting in hypertrophic growth of myocytes after -or ß-AR-stimulation are established, the functional consequences of hypertrophy on contractility of cardiomyocytes are less analysed. The present study investigates whether -or ß-AR-stimulation by phenylephrine (PE, 10 µM) or isoprenaline (ISO, 1 µM) over 24 h modifies cell shortening in ventricular cardiomyocytes of rat. In PE-treated myocytes cell shortening under viscous load (400 cP) at 0.5 Hz was reduced from 7.2±0.4 % to 4.8±0.6 % (n=12, p<0.01). At 2.0 Hz this reduction was compensated by an increased relaxation velocity (137±15 µm/s vs. 181±36 µm/s, p<0.05). In parallel, SERCA2A protein increased 2.3±0.3 fold and mRNA 1.9±0.4 fold vs. unstimulated controls (p<0.05). This induction was independent of PKC activation but depended on an increase in diastolic calcium. As downstream target the calcineurin/NFAT pathway was identified, since addition of BAPTA, cyclosporine or NFAT-decoy oligonucleotides reduced SERCA2A expression in presence of PE. Under ß-AR stimulation similar effects were found: SERCA expression increased by 63.7 ± 6.5 % under ISO stimulation (n=7, p<0.05) and could be reduced to basal levels by NFAT decoy oligos. Decreased cell shortening under ISO is found at 0.5 Hz, but not at high beating frequencies (2 Hz). In myocytes, transformed with NFAT-decoy oligos, decreased cell shortening is present also at 2 Hz under ß-adrenergic stimulation. In conclusion, a functional deficit in contraction of cardiomyocytes due to PE or ISO stimulation can be partially antagonized by PE- or ISO-dependent activation of SERCA expression mediated via the calcium/calcineurin/NFAT pathway.

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Attia, A. Articles by Euler, G PubMed Articles by Attia, A. Articles by Euler, G