Regional expression of phospholamban in the human heart

Peter Bokník, Claus Unkel, Uwe Kirchhefer, Ulrich Kleideiter, Oliver Klein-Wiele, Jörg Knapp, Bettina Linck, Hartmut Lüss, Frank Ulrich Müller, Wilhelm Schmitz, Ute Vahlensieck, Norbert Zimmermann, Larry R. Jones, Joachim Neumann

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49 Scopus citations

Abstract

Background: Several independent lines of evidence indicate that phospholamban (PLB) expression correlates positively with depression of force of contraction and duration of contraction in isolated cardiac preparations of several animal species. Here, we studied whether PLB levels correlate with attenuation of contractility and enhancement of contractile time parameters in different parts of the human heart. Methods: Force of contraction was measured in isolated electrically driven atrial and ventricular preparations from human hearts. Ca2+-uptake by human atrial and ventricular homogenates was assayed at different ionized Ca2+-concentrations. Protein expression of PLB and the sarcoplasmic Ca2+-ATPase (SERCA) was measured in homogenates by quantitative immunoblotting using specific antibodies. PLB mRNA expression was quantified in human cardiac preparations by Northern blot analysis. Results: The duration of contraction in isolated preparations of human right ventricle (RV) was double that found in right atrial preparations (RA) (620±25 ms versus 308±15 ms). In RA, PLB expression was reduced by 44% at the protein level and by 34% at the mRNA level compared to RV. In contrast, the SERCA protein content was increased by 104% in RA compared to RV. Ca2+- uptake at low ionized Ca2+-concentration, where the inhibiting effect of PLB is maximal, amounted to 1.39±0.28 nmol Ca2+/mg protein in RA and to 0.62±0.09 nmol Ca2+/mg protein in RV (n=6 both). Conclusions: It is suggested that duration of contraction is shorter in human atrium versus ventricle due to the combined effect of decreased PLB levels (which inhibits SERCA function) and increased SERCA levels. The lower relative ratio of PLB to SERCA leads to less inhibition of SERCA and increased Ca2+-uptake which enhances relaxation and contraction in human atrium.

Original languageEnglish (US)
Pages (from-to)67-76
Number of pages10
JournalCardiovascular research
Volume43
Issue number1
DOIs
StatePublished - Jul 1 1999

Keywords

  • Atrial function
  • Contractile function
  • Gene expression
  • SR (function)
  • Ventricular function

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Bokník, P., Unkel, C., Kirchhefer, U., Kleideiter, U., Klein-Wiele, O., Knapp, J., Linck, B., Lüss, H., Ulrich Müller, F., Schmitz, W., Vahlensieck, U., Zimmermann, N., Jones, L. R., & Neumann, J. (1999). Regional expression of phospholamban in the human heart. Cardiovascular research, 43(1), 67-76. https://doi.org/10.1016/S0008-6363(99)00053-X