Effects of isoproterenol on twitch contraction of wild type and phospholamban-deficient murine ventricular myocardium

Bo Sheng Pan, James D. Hannon, Richard Wiedmann, James D. Potter, Evangelia G. Kranias, You Tang Shen, Robert G. Johnson, Philippe R. Housmans

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Ablation of the gene for phospholamban (PLB), a transmembrane peptide regulator for the cardiac sarcoplasmic reticulum Ca2+ pump, in mice brings about a complete loss of the myocardial responses to β-adrenergic agonists. We have evaluated the functional significance of PLB-independent mechanisms in the myocardial responses to β-adrenergic stimulation in isolated intact ventricular myocardium. We compared the effects of (-)-isoproterenol (ISO) on isometric twitch contraction of paced right ventricular muscle strips of wild type (WT) and PLB-deficient (PLBKO) mice. At 37°C, frequent spontaneous contractions in both types of muscles required the inclusion of lidocaine, an antiarrhythmic, in the bathing medium. Thus the experiments were also performed at two lower temperatures, 30°C and 25°C, at which lidocaine was not needed. Under three conditions, in the absence of ISO, PLBKO ventricular muscles exhibited substantially shortened time to peak tension (TPT) and half relaxation time (TR(1/2)), compared with the WT muscles. In both WT and PLBKO muscles ISO increased the peak developed tension and decreased TPT and TR(1/2) in a dose-dependent manner although the effects were generally smaller in PLBKO than in WT muscles. One micromolar ISO caused TPT and TR(1/2) to decrease by 7.3 ± 1.2% (mean ± SEM) and 7.5 ± 1.2% in PLBKO vs. 22.8 ± 0.7% and 29.1 ± 1.7% in WT at 37°C; by 13.5 ± 0.4% and 14.1 ± 1.2% in PLBKO vs. 31.3 ± 0.8% and 44.8 ± 1.3% in WT at 30°C; by 15.0 ± 2.3% and 21.1 ± 4.9% in PLBKO vs. 25.8 ± 1.9% and 54.0 ± 1.9% in WT at 25°C. These findings strongly suggest that PLB-independent mechanisms play a significant role in mediating the positive inotropic and lusitropic effects of β-adrenergic agonists on ventricular myocardium.

Original languageEnglish (US)
Pages (from-to)159-166
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume31
Issue number1
DOIs
StatePublished - Jan 1999

Keywords

  • Excitation-contraction coupling
  • Isoproterenol
  • Myocardium
  • Phospholamban
  • Relaxation
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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    Pan, B. S., Hannon, J. D., Wiedmann, R., Potter, J. D., Kranias, E. G., Shen, Y. T., Johnson, R. G., & Housmans, P. R. (1999). Effects of isoproterenol on twitch contraction of wild type and phospholamban-deficient murine ventricular myocardium. Journal of Molecular and Cellular Cardiology, 31(1), 159-166. https://doi.org/10.1006/jmcc.1998.0854