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 journalArticle

45 Citations (Scopus)

Abstract

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
Volume30
Issue number7
DOIs
StatePublished - Jul 1998
Externally publishedYes

Fingerprint

Ryanodine
Aequorin
Sarcoplasmic Reticulum
Myocardium
Light
Muscles

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Frequency-dependent changes in contribution of SR Ca2+ to Ca2+ transients in failing human myocardium assessed with ryanodine. / Schlotthauer, Klaus; Schattmann, Jörg; Bers, Donald M; Maier, Lars S.; Schütt, Ulrich; Minami, Kizatomo; Just, Hanjörg; Hasenfuss, Gerd; Pieske, Burkert.

In: Journal of Molecular and Cellular Cardiology, Vol. 30, No. 7, 07.1998, p. 1285-1294.

Research output: Contribution to journalArticle

Schlotthauer, Klaus ; Schattmann, Jörg ; Bers, Donald M ; Maier, Lars S. ; Schütt, Ulrich ; Minami, Kizatomo ; Just, Hanjörg ; Hasenfuss, Gerd ; Pieske, Burkert. / Frequency-dependent changes in contribution of SR Ca2+ to Ca2+ transients in failing human myocardium assessed with ryanodine. In: Journal of Molecular and Cellular Cardiology. 1998 ; Vol. 30, No. 7. pp. 1285-1294.
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AU - Schattmann, Jörg

AU - Bers, Donald M

AU - Maier, Lars S.

AU - Schütt, Ulrich

AU - Minami, Kizatomo

AU - Just, Hanjörg

AU - Hasenfuss, Gerd

AU - Pieske, Burkert

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AB - 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.

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