Frequency-dependent changes in contribution of SR Ca2+ to Ca2+ transients in failing human myocardium assessed with ryanodine

Klaus Schlotthauer, Jörg Schattmann, Donald M Bers, Lars S. Maier, Ulrich Schütt, Kizatomo Minami, Hanjörg Just, Gerd Hasenfuss, Burkert Pieske

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


We tested the influence of blocking sarcoplasmic reticulum (SR) function with ryanodine (1 μM) on stimulation rate-dependent changes of intracellular Ca2+ transients and twitch force in failing human myocardium. Isometrically contracting, electrically stimulated muscle strips from ventricles of 10 end-stage failing human hearts were used. Muscles were loaded with the intracellular Ca2+ indicator aequorin. At stimulation rates from 0.5-3 Hz, intracellular Ca2+ transients and twitch force were simultaneously recorded before and after ryanodine exposure (37°C). Ryanodine significantly reduced twitch force at 1 Hz by 46 ± 9% and aequorin light by 57 ± 10% in failing human myocardium (P < 0.05). The blunted or inverse aequorin light- and force-frequency relation became positive after ryanodine: in failing human myocardium, twitch force and aequorin light before ryanodine did not increase with increasing frequency and force decreased significantly at 3 Hz (P < 0.05). After ryanodine, twitch force (P < 0.05) and aequorin light increased with increasing stimulation frequency and were maximum at 2 Hz. The data indicate that inhibition of SR function significantly reduces twitch force and Ca2+ transients in failing human myocardium, but converts the blunted or inverse Ca2+- and force-frequency relation into a positive one. We infer that Ca2+ responsible for ~ 50% of twitch force is derived from the SR and ~ 50% from sarcolemmal Ca2+ influx in failing human myocardium. This sarcolemmal component increases at higher stimulation frequencies.

Original languageEnglish (US)
Pages (from-to)1285-1294
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Issue number7
StatePublished - Jul 1998
Externally publishedYes


  • Aequorin
  • Excitation-contraction coupling
  • Force-frequency relation
  • Human myocardium
  • Ryanodine

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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