scholarly journals Modification of sarcoplasmic reticulum (SR) Ca2+ release by FK506 induces defective excitation-contraction coupling only when SR Ca2+ recycling is disturbed

2005 ◽  
Vol 83 (4) ◽  
pp. 357-366 ◽  
Author(s):  
Shu Yoshihara ◽  
Hiroshi Satoh ◽  
Masao Saotome ◽  
Hideki Katoh ◽  
Hajime Terada ◽  
...  
Keyword(s):  
Steady State ◽  
Sarcoplasmic Reticulum ◽  
Normal Condition ◽  
Binding Protein ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Cell Shortening ◽  
Fk506 Binding Protein ◽  
Ec Coupling ◽  
Protein Dissociation

This study examined whether the effects of FK506-binding protein dissociation from sarcoplasmic reticulum (SR) Ca2+ release channels on excitation-contraction (EC) coupling changed when SR Ca2+ reuptake and (or) the trans-sarcolemmal Ca2+ extrusion were altered. The steady-state twitch Ca2+ transient (CaT), cell shortening, post-rest caffeine-induced CaT, and Ca2+ sparks were measured in rat ventricular myocytes using laser-scanning confocal microscopy. In the normal condition, 50 µmol FK506/L significantly increased steady-state CaT, cell shortening, and post-rest caffeine-induced CaT. When the cells were solely perfused with thapsigargin, FK506 did not reduce any of the states, but when low [Ca2+]0 (0.1 mmol/L) was perfused additionally, FK506 reduced CaT and cell shortening, and accelerated the reduction of post-rest caffeine-induced CaT. FK506 significantly increased Ca2+ spark frequency in the normal condition, whereas it mainly prolonged duration of individual Ca2+ sparks under the combination of thapsigargin and low [Ca2+]0 perfusion. Modification of SR Ca2+ release by FK506 impaired EC coupling only when released Ca2+ could not be taken back into the SR and was readily extruded to the extracellular space. Our findings could partly explain the controversy regarding the contribution of FK506-binding protein dissociation to defective EC coupling.Key words: FK506, ryanodine receptor, sarcoplasmic reticulum Ca2+-ATPase, Na+/Ca2+ exchange, excitation-contraction coupling

Frog ventricle: participation of SR in excitation-contraction coupling

1989 ◽  
Vol 256 (5) ◽  
pp. H1432-H1439
Author(s):  
M. E. Anderson ◽  
I. J. Fox ◽  
C. R. Swayze ◽  
S. K. Donaldson
Keyword(s):  
Steady State ◽  
Sarcoplasmic Reticulum ◽  
Inhibitory Effects ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Resting Tension ◽  
Mammalian Myocardium ◽  
Frog Myocardium ◽  
Frog Ventricle ◽  
Important Site

Activation of the first beat (B1) following a 60-s pause is diminished in isometrically contracting frog ventricular strips, in contrast to the augmentation documented for sarcoplasmic reticulum (SR)-dependent mammalian myocardium. However, treatment of frog ventricular strips with ouabain, an indirect inhibitor of the sarcolemmal Na+-Ca2+ exchanger, selectively enhanced postpause beats suggesting that in the absence of ouabain significant extrusion of cellular Ca2+ occurred during the pause. Because resting tension did not increase during the pause in ouabain-treated strips, the nonextruded Ca2+ must have been sequestered into a compartment such as SR. Steady-state beats were not affected by ouabain; its actions appeared to be separate from its known positive inotropism. Caffeine, a direct SR stimulus, initially enhanced B1 and subsequently decreased activation of all beats, which was consistent with initial augmentation of SR Ca2+ release and subsequent depletion of SR Ca2+ stores. Ouabain both potentiated the stimulatory effects and blocked the inhibitory effects of caffeine, suggesting that ouabain increased Ca2+ stores in the same intracellular Ca2+ pool as that acted on by caffeine, the SR. Ryanodine, an inhibitor of SR in mammalian myocardium, did not affect activation of frog myocardium. SR may be an important site for activator Ca2+ cycling in frog myocardium under control conditions as well as after long diastolic intervals in the presence of ouabain.

scholarly journals Over-expression of FK506-binding protein FKBP12.6 alters excitation-contraction coupling in adult rabbit cardiomyocytes

2004 ◽  
Vol 556 (3) ◽  
pp. 919-934 ◽  
Author(s):  
C. M. Loughrey ◽  
T. Seidler ◽  
S. L. W. Miller ◽  
J. Prestle ◽  
K. E. MacEachern ◽  
...  
Keyword(s):  
Binding Protein ◽  
Adult Rabbit ◽  
Excitation Contraction Coupling ◽  
Over Expression ◽  
Contraction Coupling ◽  
Fk506 Binding Protein

scholarly journals Dantrolene suppresses spontaneous Ca2+ release without altering excitation-contraction coupling in cardiomyocytes of aged mice

2014 ◽  
Vol 307 (6) ◽  
pp. H818-H829 ◽  
Author(s):  
Timothy L. Domeier ◽  
Cale J. Roberts ◽  
Anne K. Gibson ◽  
Laurin M. Hanft ◽  
Kerry S. McDonald ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Dysfunction ◽  
Wave Amplitude ◽  
Left Ventricular ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Aged Mice ◽  
Cell Shortening ◽  
Antiarrhythmic Effects ◽  
Young Mice

Cardiac dysfunction in the aged heart reflects abnormalities in cardiomyocyte Ca2+ homeostasis including altered Ca2+ cycling through the sarcoplasmic reticulum (SR). The ryanodine receptor antagonist dantrolene exerts antiarrhythmic effects by preventing spontaneous diastolic Ca2+ release from the SR. We tested the hypothesis that dantrolene prevents spontaneous Ca2+ release without altering excitation-contraction coupling in aged myocardium. Left ventricular cardiomyocytes isolated from young (3 to 4 mo) and aged (24–26 mo) C57BL/6 mice were loaded with the Ca2+ indicator fluo-4. Amplitudes of action potential-induced Ca2+ transients at 1-Hz pacing were similar between young and aged mice, yet cell shortening was impaired in aged mice. Isoproterenol (1 μM) increased Ca2+ transient amplitude and cell shortening to identical levels in young and aged; dantrolene (1 μM) had no effect on Ca2+ transients or cell shortening during pacing. Under Ca2+ overload conditions induced with 10 mM extracellular Ca2+ concentration, spontaneous Ca2+ waves were of diminished amplitude and associated with lower SR Ca2+ content in aged versus young mice. Despite no effect in young mice, dantrolene increased SR Ca2+ content and Ca2+ wave amplitude in aged mice. In the presence of isoproterenol following rest from 1-Hz pacing, Ca2+ spark frequency was elevated in aged mice, yet the time to spontaneous Ca2+ wave was similar between young and aged mice; dantrolene decreased Ca2+ spark frequency and prolonged the time to Ca2+ wave onset in aged mice with no effect in young mice. Thus dantrolene attenuates diastolic Ca2+ release in the aged murine heart that may prove useful in preventing cardiac dysfunction.

Calmodulin and Excitation-Contraction Coupling

Physiology ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 281-284 ◽  
Author(s):  
Susan L. Hamilton ◽  
Irina Serysheva ◽  
Gale M. Strasburg
Keyword(s):  
Skeletal Muscle ◽  
Ion Channels ◽  
Sarcoplasmic Reticulum ◽  
Release Channel ◽  
Excitation Contraction Coupling ◽  
Transverse Tubule ◽  
Contraction Coupling ◽  
Voltage Dependent ◽  
Important Regulator ◽  
Precise Role

Excitation-contraction coupling in cardiac and skeletal muscle involves the transverse-tubule voltage-dependent Ca2+ channel and the sarcoplasmic reticulum Ca2+ release channel. Both of these ion channels bind and are modulated by calmodulin in both its Ca2+-bound and Ca2+-free forms. Calmodulin is, therefore, potentially an important regulator of excitation-contraction coupling. Its precise role, however, has not yet been defined.

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