Details

Autor(en) / Beteiligte

• Bolck, Birgit
• Munch, Gotz
• Mackenstein, Peter
• Hellmich, Martin
• Hirsch, Ingo
• Reuter, Hannes
• Hattebuhr, Nadja
• Weig, Hans-Jorg
• Ungerer, Martin
• Brixius, Klara
• Schwinger, Robert H. G

Titel

Na+/Ca2+ exchanger overexpression impairs frequency- and ouabain-dependent cell shortening in adult rat cardiomyocytes

Ist Teil von

• American journal of physiology. Heart and circulatory physiology, 2004-10, Vol.287 (4), p.H1435-H1445

Ort / Verlag

United States

Erscheinungsjahr

2004

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• 1 Laboratory of Muscle Research and Molecular Cardiology, Department for Internal Medicine III, University of Cologne, 50924 Cologne; 2 Deutsches Herzzentrum der Technischen Universität München, 81675 München; and 3 Institute of Medical Statistics, Informatics, and Epidemiology; University of Cologne, 50924 Cologne, Germany Submitted 3 May 2003 ; accepted in final form 18 May 2004 The Na + /Ca 2+ exchanger (NCX) may influence cardiac function depending on its predominant mode of action, forward mode or reverse mode, during the contraction-relaxation cycle. The intracellular Na + concentration ([Na + ] i ) and the duration of the action potential as well as the level of NCX protein expression regulate the mode of action of NCX. [Na + ] i and NCX expression have been reported to be increased in human heart failure. Nevertheless, the consequences of altered NCX expression in heart failure are still a matter of discussion. We aimed to characterize the influence of NCX expression on intracellular Ca 2+ transport in rat cardiomyocytes by adenoviral-mediated gene transfer. A five- to ninefold (dose dependent) overexpression of NCX protein was achieved after 48 h by somatic gene transfer (Ad.NCX.GFP) versus control (Ad.GFP). NCX activity, determined by Na + gradient-dependent 45 Ca 2+ -uptake, was significantly increased. The protein expressions of sarco(endo)plasmic reticulum Ca 2+ -ATPase, phospholamban, and calsequestrin were unaffected by NCX overexpression. Fractional shortening (FS) of isolated cardiomyocytes was significantly increased at low stimulation rates in Ad.NCX.GFP. After a step-wise enhancing frequency of stimulation to 3.0 Hz, FS remained unaffected in Ad.GFP cells but declined in Ad.NCX.GFP cells. The positive inotropic effect of the cardiac glycoside ouabain was less effective in Ad.NCX.GFP cells, whereas the positive inotropic effect of -adrenergic stimulation remained unchanged. In conclusion, NCX overexpression results in a reduced cell shortening at higher stimulation frequencies as well as after inhibition of sarcolemmal Na + -K + -ATPase, i.e., in conditions with enhanced [Na + ] i . At low stimulation rates, increased NCX expression enhances both intracellular systolic Ca 2+ and contraction amplitude. adenovirus; gene transfer; calcium cycling; sarcoplasmic reticulum; contractility Address for reprint requests and other correspondence: R. H. G. Schwinger, Laboratory of Muscle Research and Molecular Cardiology, Dept. of Internal Medicine III, Univ. of Cologne, Joseph-Stelzmann Strasse 9, 50924 Cologne, Germany (E-mail: Robert.Schwinger{at}medizin.Uni-Koeln.de )