Basic Research in Cardiology

, Volume 92, Supplement 1, pp 75–86 | Cite as

Ca2+-dependent and Ca2+-independent regulation of contractility in isolated human myocardium

  • B. Pieske
  • K. Schlotthauer
  • J. Schattmann
  • F. Beyersdorf
  • J. Martin
  • H. Just
  • G. Hasenfuss
Article

Abstract

Changes in contractile force of the myocardium may depend on changes in the intracellular Ca2+ concentration, changes in the responsiveness of the myofibrils for Ca2+, or a combination of both. We investigated in isolated muscle strip preparations from human nonfailing and endstage failing hearts the influence of physical (changes in preload, stimulation rate, or rhythm), and pharmacological interventions (α-or β-adrenoceptor-stimulation, endothelin) on developed force of contraction and the corresponding intracellular Ca2+ transients.

Methods

Isometric contraction, electrical stimulation, 37°C. Simultaneous registration of force of contraction and intracellular Ca2+ transients (aequorin method).

Results

Increases in preload, α-and endothelin-receptor stimulation resulted in increases in force of contraction without increasing aequorin light emission. Increasing stimulation rate or increasing rest intervals resulted in parallel increases (nonfailing myocardium) or decreases (failing myocardium) of force of contraction and aequorin light emission. β-Adrenoceptor-stimulation exerted inotropic and lusitropic effects in human failing myocardium associated with a large, overproportional increase in aequorin light emission.

Conclusion

The human heart regulates intrinsic contractility via several subcellular mechanisms. Increases in preload (Frank-Starling-mechanism) and α-or endothelin-receptor-stimulation enhance myocardial contractility by increasing the Ca2+ responsiveness of the myofilaments; rate- and rhythm-dependent modulation of the contractile state directly depend on changes in the intracellular Ca2+-transients; β-adrenoceptor stimulation results in an overproportional large increase in intracellular Ca2+ transients, preably due to additional cAMP-dependent Ca2+-desensitizing effects on the level of the myofibrils.

Key words

Human myocardium excitation-contraction coupling Frank-Starling mechanism endothelin aequorin 

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Copyright information

© Steinkopff Verlag 1997

Authors and Affiliations

  • B. Pieske
    • 1
  • K. Schlotthauer
    • 1
  • J. Schattmann
    • 1
  • F. Beyersdorf
    • 2
  • J. Martin
    • 2
  • H. Just
    • 1
  • G. Hasenfuss
    • 1
  1. 1.Medizinische Klinik III Abteilung Kardiologie und AngiologieUniversität FreiburgFreiburgGermany
  2. 2.Medizinische Klinik III Abteilung Herz-und GefäßchirurgieUniversität FreiburgFreiburgGermany

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