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 language | English (US) |
|---|---|
| Pages (from-to) | 1285-1294 |
| Number of pages | 10 |
| Journal | Journal of Molecular and Cellular Cardiology |
| Volume | 30 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1998 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Frequency-dependent changes in contribution of SR Ca2+ to Ca2+ transients in failing human myocardium assessed with ryanodine
AU - Schlotthauer, Klaus
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
PY - 1998/7
Y1 - 1998/7
N2 - 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.
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.
KW - Aequorin
KW - Excitation-contraction coupling
KW - Force-frequency relation
KW - Human myocardium
KW - Ryanodine
UR - http://www.scopus.com/inward/record.url?scp=0032128443&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032128443&partnerID=8YFLogxK
U2 - 10.1006/jmcc.1998.0690
DO - 10.1006/jmcc.1998.0690
M3 - Article
C2 - 9710797
AN - SCOPUS:0032128443
VL - 30
SP - 1285
EP - 1294
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 7
ER -