Inhibition of carnitine synthesis modulates protein contents of the cardiac sarcoplasmic reticulum Ca 2+ -ATPase and hexokinase type I in rat hearts with myocardial infarction

2000 ◽  
Vol 95 (5) ◽  
pp. 343-348 ◽  
Author(s):  
Katsunori Yonekura ◽  
Yoko Eto ◽  
Ikuo Yokoyama ◽  
Akihiro Matsumoto ◽  
Seiryo Sugiura ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Sarcoplasmic Reticulum ◽  
Type I ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Rat Hearts ◽  
Hexokinase Type I

scholarly journals Effects of sarcoplasmic reticulum Ca2+-ATPase overexpression in postinfarction rat myocytes

2005 ◽  
Vol 98 (6) ◽  
pp. 2169-2176 ◽  
Author(s):  
Belinda A. Ahlers ◽  
Jianliang Song ◽  
JuFang Wang ◽  
Xue-Qian Zhang ◽  
Lois L. Carl ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Sarcoplasmic Reticulum ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Transport Pathways ◽  
Rat Hearts ◽  
Intracellular Ca ◽  
Rat Myocytes ◽  
Fractional Shortening ◽  
Expression And Activity

Previous studies in adult myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) demonstrated abnormal contractility and intracellular Ca2+ concentration ([Ca2+]i) homeostasis and decreased sarcoplasmic reticulum Ca2+-ATPase (SERCA2) expression and activity, but sarcoplasmic reticulum Ca2+ leak was unchanged. In the present study, we investigated whether SERCA2 overexpression in MI myocytes would restore contraction and [Ca2+]i transients to normal. Compared with sham-operated hearts, 3-wk MI hearts exhibited significantly higher left ventricular end-diastolic and end-systolic volumes but lower fractional shortening and ejection fraction, as measured by M-mode echocardiography. Seventy-two hours after adenovirus-mediated gene transfer, SERCA2 overexpression in 3-wk MI myocytes did not affect Na+-Ca2+ exchanger expression but restored the depressed SERCA2 levels toward those measured in sham myocytes. In addition, the reduced sarcoplasmic reticulum Ca2+ uptake in MI myocytes was improved to normal levels by SERCA2 overexpression. At extracellular Ca2+ concentration of 5 mM, the subnormal contraction and [Ca2+]i transient amplitudes in MI myocytes (compared with sham myocytes) were restored to normal by SERCA2 overexpression. However, at 0.6 mM extracellular Ca2+ concentration, the supernormal contraction and [Ca2+]i transient amplitudes in MI myocytes (compared with sham myocytes) were exacerbated by SERCA2 overexpression. We conclude that SERCA2 overexpression was only partially effective in ameliorating contraction and [Ca2+]i transient abnormalities in our rat model of ischemic cardiomyopathy. We suggest that other Ca2+ transport pathways, e.g., Na+-Ca2+ exchanger, may also play an important role in contractile and [Ca2+]i homeostatic abnormalities in MI myocytes.

Cyclosporin A treatment alters characteristics of Ca2+-release channel in cardiac sarcoplasmic reticulum

1999 ◽  
Vol 276 (3) ◽  
pp. H865-H872 ◽  
Author(s):  
Kyoung Sik Park ◽  
Tae Kon Kim ◽  
Do Han Kim
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cyclosporin A ◽  
Skeletal Muscles ◽  
Molecular Mechanisms ◽  
Ruthenium Red ◽  
Release Channel ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Physiological Alterations ◽  
Rat Hearts ◽  
Dose Dependent

Chronic treatment with cyclosporin A (CsA) has been reported (H. S. Banijamali, M. H. ter Keurs, L. C. Paul, and H. E. ter Keurs. Cardiovasc. Res. 27: 1845–1854, 1993; I. Kingma, E. Harmsen, H. E. ter Keurs, H. Benediktsson, and L. C. Paul. Int. J. Cardiol. 31: 15–22, 1991) to induce reversible alterations of contractile properties in rat hearts. To define the molecular mechanisms underlying the physiological alterations, the Ca2+-release channel (CRC) and Ca2+-ATPase from sarcoplasmic reticulum in rats were examined. Ryanodine binding to whole homogenates of rat hearts shows time- and dose-dependent alterations in CRC properties by CsA. On 3 wk of treatment with 15 mg CsA ⋅ kg body wt−1 ⋅ day−1, 1) maximal ryanodine binding (Bmax) decreased, 2) the dissociation constant of ryanodine ( K d) increased, 3) caffeine sensitivity of CRC increased, and 4) ruthenium red sensitivity of CRC decreased. On the other hand, Bmax and K d of ryanodine binding in rat skeletal muscles were not changed. Ryanodine-sensitive oxalate-supported Ca2+ uptake in whole homogenates was lower in CsA-treated rat hearts than in control hearts, whereas total Ca2+ uptake in the presence of 500 M ryanodine was not changed. Functional experiments with rapamycin and Western blot analysis suggest that the CsA-induced alteration of ryanodine binding is due at least in part to an upregulation of calcineurin. The heart muscle-specific alterations of CRC could be responsible for the previously reported contractile changes of CsA-treated rat hearts.

scholarly journals Effects of impaired Ca2+homeostasis on contraction in postinfarction myocytes

1999 ◽  
Vol 86 (3) ◽  
pp. 943-950 ◽  
Author(s):  
Xue-Qian Zhang ◽  
Timothy I. Musch ◽  
Robert Zelis ◽  
Joseph Y. Cheung
Keyword(s):  
Myocardial Infarction ◽  
Steady State ◽  
Membrane Potential ◽  
Sarcoplasmic Reticulum ◽  
Mechanical Activity ◽  
Half Time ◽  
Rat Hearts ◽  
Rat Myocytes ◽  
State Contraction ◽  
Exchange Activity

The significance of altered Ca2+ influx and efflux pathways on contractile abnormalities of myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) was investigated by varying extracellular Ca2+concentration ([Ca2+]o, 0.6–5.0 mM) and pacing frequency (0.1–5.0 Hz). Myocytes isolated from 3-wk MI hearts were significantly longer than those from sham-treated (Sham) hearts (125 ± 1 vs. 114 ± 1 μm, P < 0.0001). At high [Ca2+]oand low pacing frequency, conditions that preferentially favored Ca2+ influx over efflux, Sham myocytes shortened to a greater extent than 3-wk MI myocytes. Conversely, under conditions that favored Ca2+ efflux (low [Ca2+]oand high pacing frequency), MI myocytes shortened more than Sham myocytes. At intermediate [Ca2+]oand pacing frequencies, differences in steady-state contraction amplitudes between Sham and MI myocytes were no longer significant. Collectively, the interpretation of these data was that Ca2+ influx and efflux pathways were subnormal in MI myocytes and that they contributed to abnormal cellular contractile behavior. Because Na+/Ca2+exchange activity, but not whole cell Ca2+ current, was depressed in 3-wk MI rat myocytes, our results on steady-state contraction are consistent with, but not proof of, the hypothesis that depressed Na+/Ca2+exchange accounted for abnormal contractility in MI myocytes. The effects of depressed Na+/Ca2+exchange on MI myocyte mechanical activity were further evaluated in relaxation from caffeine-induced contractures. Because Ca2+ uptake by sarcoplasmic reticulum was inhibited by caffeine and with the assumption that intracellular Na+ and membrane potential were similar between Sham and MI myocytes, myocyte relaxation from caffeine-induced contracture can be taken as an estimate of Ca2+ extrusion by Na+/Ca2+exchange. In MI myocytes, in which Na+/Ca2+exchange activity was depressed, the half time of relaxation (1.54 ± 0.14 s) was significantly ( P < 0.02) prolonged compared with that measured in Sham myocytes (1.10 ± 0.10 s).

In situ SR function in postinfarction myocytes

1999 ◽  
Vol 87 (6) ◽  
pp. 2143-2150 ◽  
Author(s):  
Xue-Qian Zhang ◽  
Yuk-Chow Ng ◽  
Russell L. Moore ◽  
Timothy I. Musch ◽  
Joseph Y. Cheung
Keyword(s):  
Myocardial Infarction ◽  
Sarcoplasmic Reticulum ◽  
Half Time ◽  
Time Constants ◽  
Rat Hearts ◽  
Intracellular Ca ◽  
Rat Myocytes ◽  
Electrophysiological Technique ◽  
Empirical Constants

Previous studies have shown lower systolic intracellular Ca2+ concentrations ([Ca2+]i) and reduced sarcoplasmic reticulum (SR)-releasable Ca2+ contents in myocytes isolated from rat hearts 3 wk after moderate myocardial infarction (MI). Ca2+ entry via L-type Ca2+ channels was normal, but that via reverse Na+/Ca2+exchange was depressed in 3-wk MI myocytes. To elucidate mechanisms of reduced SR Ca2+ contents in MI myocytes, we measured SR Ca2+uptake and SR Ca2+ leak in situ, i.e., in intact cardiac myocytes. For sham and MI myocytes, we first demonstrated that caffeine application to release SR Ca2+ and inhibit SR Ca2+ uptake resulted in a 10-fold prolongation of half-time ( t ½) of [Ca2+]itransient decline compared with that measured during a normal twitch. These observations indicate that early decline of the [Ca2+]itransient during a twitch in rat myocytes was primarily mediated by SR Ca2+-ATPase and that the t ½ of [Ca2+]idecline is a measure of SR Ca2+uptake in situ. At 5.0 mM extracellular Ca2+, systolic [Ca2+]iwas significantly ( P ≤ 0.05) lower (337 ± 11 and 416 ± 18 nM in MI and sham, respectively) and t ½ of [Ca2+]idecline was significantly longer (0.306 ± 0.014 and 0.258 ± 0.014 s in MI and sham, respectively) in MI myocytes. The 19% prolongation of t ½ of [Ca2+]i decline was associated with a 23% reduction in SR Ca2+-ATPase expression (detected by immunoblotting) in MI myocytes. SR Ca2+ leak was measured by a novel electrophysiological technique that did not require assigning empirical constants for intracellular Ca2+buffering. SR Ca2+ leak rate was not different between sham and MI myocytes: the time constants of SR Ca2+ loss after thapsigargin were 290 and 268 s, respectively. We conclude that, independent of decreased SR filling by Ca2+ influx, the lower SR Ca2+ content in MI myocytes was due to reduced SR Ca2+ uptake and SR Ca2+-ATPase expression, but not to enhanced SR Ca2+ leak.

Regulatory role of ovarian sex hormones in calcium uptake activity of cardiac sarcoplasmic reticulum

2006 ◽  
Vol 291 (3) ◽  
pp. H1101-H1108 ◽  
Author(s):  
Tepmanas Bupha-Intr ◽  
Jonggonnee Wattanapermpool
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Sex Hormones ◽  
Mrna Level ◽  
Left Ventricular ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Female Sex Hormones ◽  
Rat Hearts ◽  
Intracellular Ca ◽  
Uptake Activity ◽  
First Time

Alterations in the intracellular Ca2+ handling in cardiomyocytes may underlie the cardiac dysfunction observed in the ovarian sex hormone-deprived condition. To test the hypothesis that ovarian sex hormones had a significant role in the cardiac intracellular Ca2+ mobilization, the sarcoplasmic reticulum (SR) Ca2+ uptake and SR Ca2+-ATPase (SERCA) activity were determined in 10-wk ovariectomized rat hearts. With the use of left ventricular homogenate preparations, a significant suppression of maximum SR Ca2+ uptake activity, but with an increase in SR Ca2+ responsiveness, was demonstrated in ovariectomized hearts. In parallel measurements of SERCA activity in SR-enriched membrane preparations from ovariectomized hearts, a suppressed maximum SERCA activity with a leftward shift in the relationship between pCa (-log molar free Ca2+ concentration) and SERCA activity was also detected. A significant downregulation of SERCA proteins and reduction in the SERCA mRNA level were observed in association with suppressed maximum SERCA activity. While there were no changes in total phospholamban and phosphorylated Ser16 phospholamban levels, a decrease in phosphorylated Thr17 phospholamban as well as an increase in the suprainhibitory, monomeric form of phospholamban stoichiometry was found. Estrogen and progesterone supplementations were equally effective in preventing changes in ovariectomized hearts. Our data showed for the first time that female sex hormones played an important role in the regulation of the cardiac SR Ca2+ uptake. Under hormone-deficient conditions, there was an adaptive response of SERCA that escaped the regulatory effect of phospholamban.

Sign in / Sign up

Export Citation Format

Share Document