Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schlotthauer, K; Schattmann, J; Bers, DM; Maier, LS; Schütt, U; Minami, K; Just, H; Hasenfuss, G; Pieske, B.
Frequency-dependent changes in contribution of SR Ca2+ to Ca2+ transients in failing human myocardium assessed with ryanodine.
J Mol Cell Cardiol. 1998; 30(7):1285-1294
Doi: 10.1006/jmcc.1998.0690
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- Führende Autor*innen der Med Uni Graz
- Pieske Burkert Mathias
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- Abstract:
- We tested the influence of blocking sarcoplasmic reticulum (SR) function with ryanodine (1 microM) 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 degrees 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 Ca(2+)- and force-frequency relation into a positive one. We infer that Ca2+ responsible for approximately 50% of twitch force is derived from the SR and approximately 50% from sarcolemmal Ca2+ influx in failing human myocardium. This sarcolemmal component increases at higher stimulation frequencies.
- Find related publications in this database (using NLM MeSH Indexing)
- Calcium - metabolism
- Female - metabolism
- Heart Failure, Congestive - metabolism
- Humans - metabolism
- Male - metabolism
- Middle Aged - metabolism
- Myocardial Contraction - drug effects
- Ryanodine - pharmacology
- Sarcoplasmic Reticulum - metabolism
- Find related publications in this database (Keywords)
- force-frequency relation
- ryanodine
- aequorin
- human myocardium
- excitation-contraction coupling