The role of the sarcoplasmic reticulum (sr) in the force-frequency relationship of cat and ferret ventricular muscle E. McCall, B.R. Jewell, C. Nichols, M.R. Boyett. Department of Physiology, University of Leeds, Leeds, LS2 9JT, U.K.

1988 ◽  
Vol 20 ◽  
pp. 38
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Force Frequency ◽  
Ventricular Muscle ◽  
Frequency Relationship ◽  
Relationship Of

Phospholamban-to-SERCA2 ratio controls the force-frequency relationship

1999 ◽  
Vol 276 (3) ◽  
pp. H779-H785 ◽  
Author(s):  
Markus Meyer ◽  
Wolfgang F. Bluhm ◽  
Huaping He ◽  
Steven R. Post ◽  
Frank J. Giordano ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Transgenic Mice ◽  
Cardiac Myocytes ◽  
Cardiac Contractility ◽  
Adult Rabbit ◽  
Force Frequency ◽  
Papillary Muscles ◽  
Inhibitory Protein ◽  
Frequency Relationship ◽  
Myocyte Contractility

The force-frequency relationship (FFR) describes the frequency-dependent potentiation of cardiac contractility. The interaction of the sarcoplasmic reticulum Ca2+-adenosinetriphosphatase (SERCA2) with its inhibitory protein phospholamban (PLB) might be involved in the control of the FFR. The FFR was analyzed in two systems in which the PLB-to-SERCA2 ratio was modulated. Adult rabbit cardiac myocytes were transduced with adenovirus encoding for SERCA2, PLB, and β-galactosidase (control). After 3 days, the relative PLB/SERCA2 values were significantly different between groups (SERCA2, 0.5; control, 1.0; PLB, 4.5). SERCA2 overexpression shortened relaxation by 23% relative to control, whereas PLB prolonged relaxation by 39% and reduced contractility by 47% (0.1 Hz). When the stimulation frequency was increased to 1.5 Hz, myocyte contractility was increased by 30% in control myocytes. PLB-overexpressing myocytes showed an augmented positive FFR (+78%), whereas SERCA2-transduced myocytes displayed a negative FFR (−15%). A more negative FFR was also found in papillary muscles from SERCA2 transgenic mice. These findings demonstrate that the ratio of phospholamban to SERCA2 is an important component in the control of the FFR.

Doxorubicin-induced late cardiotoxicity: delayed impairment of Ca2+-handling mechanisms in the sarcoplasmic reticulum in the rat

2000 ◽  
Vol 78 (4) ◽  
pp. 329-338 ◽  
Author(s):  
Akihito Chugun ◽  
Kyosuke Temma ◽  
Toshifumi Oyamada ◽  
Natsuyo Suzuki ◽  
Yoshinori Kamiya ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Left Atrial ◽  
Force Frequency ◽  
Ventricular Muscle ◽  
Doxorubicin Treatment ◽  
Time To Peak ◽  
Atrial Muscle ◽  
Late Cardiotoxicity ◽  
Cardiac Functions ◽  
Rat Hearts

Doxorubicin treatment causes delayed development of cardiotoxicity. Whether the doxorubicin-induced impairment of cardiac functions reverses or progresses with time after the cessation of the treatment was examined. The rats were injected with doxorubicin (2.5 mg/kg, i.v., once a week for 3 weeks) and sacrificed at 1 (1W), 13 (13W), or 18 (18W) weeks after the final doxorubicin administration. The time to peak of twitch contraction observed at 2-Hz stimulation was not altered in left atrial or ventricular muscle preparations isolated from 1W rats, but it was prolonged in those from 13W and 18W rats. The reduction of the magnitude of postrest contraction and the alteration of force-frequency relationships in left atrial muscle preparations in 1W rats were not significant, but were intensified in the 13W and 18W groups. Alterations in the postrest contraction and the force-frequency relationships in ventricular muscle preparations isolated from doxorubicin-treated rat hearts were weaker, but the pattern of alteration was similar to that observed in left atrial muscle preparations. Caffeine-induced contraction observed in skinned fibers that were isolated from the 1W rats was not altered, but it was reduced in the 18W rats. The Ca2+ sensitivity of contractile proteins was not altered in doxorubicin-treated rat hearts in any of the groups. The Kd values estimated from a [3H]ryanodine binding study were not altered, but the Bmax values were significantly lower in the 13W and 18W groups than those observed in control rats. These results suggest that the dysfunction of the sarcoplasmic reticulum progresses after the completion of doxorubicin treatment and contributes to the doxorubicin-induced late cardiotoxicity.Key words: doxorubicin, late cardiotoxicity, rat heart, sarcoplasmic reticulum.

Role of NO and PAF in the impairment of skeletal muscle contractility induced by TNF-α

2000 ◽  
Vol 279 (6) ◽  
pp. R2156-R2163 ◽  
Author(s):  
Giuseppe Alloatti ◽  
Claudia Penna ◽  
Filippo Mariano ◽  
Giovanni Camussi
Keyword(s):  
Skeletal Muscle ◽  
Methyl Ester ◽  
Platelet Activating Factor ◽  
Inhibitory Effect ◽  
No Production ◽  
Force Frequency ◽  
Muscle Contractility ◽  
Tnf Α ◽  
Frequency Relationship

The role of platelet-activating factor (PAF) and nitric oxide (NO) as mediators of the effects of tumor necrosis factor-α (TNF-α) on skeletal muscle contractility was studied in guinea pig extensor digitorum longus (EDL) muscle. TNF-α (5–10 ng/ml) reduced contractility at every stimulation frequency (1–200 Hz) and shifted the force-frequency relationship to the right. The role of NO and PAF as mediators of TNF-α was suggested by the protective effect of N G-nitro-l-arginine methyl ester (l-NAME; 1 mM), but not of N G-nitro-d-arginine methyl ester (d-NAME; 1 mM), and by the inhibitory effect of the PAF-receptor antagonist WEB-2170 (3 μM). TNF-α increased the production of PAF and NO. Similar to TNF-α, both S-nitroso- N-acetylpenicillamine (0.5–1 μM), an NO-generating compound, and PAF (10–20 nM) reduced EDL contractility. l-NAME, but not d-NAME, blocked the negative effect of PAF. Blockade of phospholipase A2, which is required for PAF synthesis, significantly reduced the effects of TNF-α. WEB-2170 inhibited NO synthesis induced by TNF-α and PAF-stimulated NO production. These results suggest that both PAF and NO contribute to the development of the mechanical alterations induced by TNF-α and that NO production is downstream to the synthesis of PAF.

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