Progress and problems in understanding the involvement of calcium in heart function

1984 ◽  
Vol 62 (7) ◽  
pp. 867-873 ◽  
Author(s):  
N. S. Dhalla ◽  
P. K. Singal ◽  
V. Panagia ◽  
J. A. C. Harrow ◽  
M. B. Anand-Srivastava ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Atpase Activity ◽  
Heart Function ◽  
Cardiac Contraction ◽  
Antiarrhythmic Agents ◽  
Functional Changes ◽  
Intracellular Ca ◽  
Cardiomyopathic Hamsters ◽  
Intracellular Storage

In this article we have briefly reviewed the role of Ca2+ in the excitation contraction coupling in the myocardium and have indicated that cardiac contraction and relaxation are initiated upon raising and lowering the intracellular concentration of free Ca2+, respectively. Different mechanisms for the entry of Ca2+ through sarcolemma as well as release of Ca2+ from sarcoplasmic reticulum and possibly mitochondria have been outlined for initiating cardiac contraction. Relaxation of the cardiac muscle appears to be intimately dependent upon efflux of Ca2+ through sarcolemma as well as sequestration of Ca2+ by the intracellular storage sites, particularly sarcoplasmic reticulum and possibly mitochondria. The actions of some pharmacological and pathophysiological interventions have been explained on the basis of changes in subcellular Ca2+ movements in myocardium. Quinidine, which produced an initial positive inotropic action on rat heart was also found to increase sarcolemmal Ca2+-ATPase activity without any changes in the Na+–K+ ATPase. Other antiarrhythmic agents, procainamide and lidocaine, also increased sarcolemmal Ca2+-ATPase activity without affecting the Na+–K+ ATPase. On the other hand, both Ca2+-ATPase and Na+–K+ ATPase activities were increased in heart sarcolemma obtained from cardiomyopathic hamsters. In this model the increased Ca2+-ATPase activity may promote the occurrence of intracellular Ca2+ overload in the cardiac cell whereas the increased Na+–K+ ATPase activity may increase Ca2+ efflux through Na+–Ca2+ exchange systems as an adaptive mechanism. It has been suggested that some caution should be exercised while interpreting the data from in vitro experiments in terms of functional changes in the myocardium. Furthermore, it has been proposed that the pathophysiology and pharmacology of Ca2+ movements at different membrane sites be understood fully in normal and diseased myocardium in order to improve the therapy of heart disease.

Scaffold topography alters intracellular calcium dynamics in cultured cardiomyocyte networks

2004 ◽  
Vol 287 (3) ◽  
pp. H1276-H1285 ◽  
Author(s):  
Lihong Yin ◽  
Harold Bien ◽  
Emilia Entcheva
Keyword(s):  
Ventricular Myocytes ◽  
Three Dimensional ◽  
Triggered Release ◽  
In Vitro System ◽  
Functional Changes ◽  
Cardiac Electromechanics ◽  
Intracellular Ca ◽  
Intracellular Calcium Dynamics ◽  
Cell Networks

Structural and functional changes ensue in cardiac cell networks when cells are guided by three-dimensional scaffold topography. We report enhanced synchronous pacemaking activity in association with slow diastolic rise in intracellular Ca2+ concentration ([Ca2+]i) in cell networks grown on microgrooved scaffolds. Topography-driven changes in cardiac electromechanics were characterized by the frequency dependence of [Ca2+]i in syncytial structures formed of ventricular myocytes cultured on microgrooved elastic scaffolds (G). Cells were electrically paced at 0.5–5 Hz, and [Ca2+]i was determined using microscale ratiometric (fura 2) fluorescence. Compared with flat (F) controls, the G networks exhibited elevated diastolic [Ca2+]i at higher frequencies, increased systolic [Ca2+]i across the entire frequency range, and steeper restitution of Ca2+ transient half-width ( n = 15 and 7 for G and F, respectively, P < 0.02). Significant differences in the frequency response of force-related parameters were also found, e.g., overall larger total area under the Ca2+ transients and faster adaptation of relaxation time to pacing rate ( P < 0.02). Altered [Ca2+]i dynamics were paralleled by higher occurrence of spontaneous Ca2+ release and increased sarcoplasmic reticulum load ( P < 0.02), indirectly assessed by caffeine-triggered release. Electromechanical instabilities, i.e., Ca2+ and voltage alternans, were more often observed in G samples. Taken together, these findings 1) represent some of the first functional electromechanical data for this in vitro system and 2) demonstrate direct influence of the microstructure on cardiac function and susceptibility to arrhythmias via Ca2+-dependent mechanisms. Overall, our results substantiate the idea of guiding cellular phenotype by cellular microenvironment, e.g., scaffold design in the context of tissue engineering.

Role of sarcoplasmic reticulum in loss of load-sensitive relaxation in pressure overload cardiac hypertrophy

1994 ◽  
Vol 266 (1) ◽  
pp. H68-H78 ◽  
Author(s):  
C. R. Cory ◽  
R. W. Grange ◽  
M. E. Houston
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Hypertrophy ◽  
Atpase Activity ◽  
Pressure Overload ◽  
Fold Increase ◽  
Left Ventricular ◽  
Isometric Tension ◽  
Tension Development ◽  
Sequestration Potential

The loss of load-sensitive relaxation observed in the pressure-overloaded heart may reflect a strategy of slowed cytosolic Ca2+ uptake to yield a prolongation of the active state of the muscle and a decrease in cellular energy expenditure. A decrease in the potential of the sarcoplasmic reticulum (SR) to resequester cytosolic Ca2+ during diastole could contribute to this attenuated load sensitivity. To test this hypothesis, both in vitro mechanical function of anterior papillary muscles and the SR Ca2+ sequestration potential of female guinea pig left ventricle were compared in cardiac hypertrophy (Hyp) and sham-operated (Sham) groups. Twenty-one days of pressure overload induced by coarctation of the suprarenal, subdiaphragmatic aorta resulted in a 36% increase in left ventricular mass in the Hyp. Peak isometric tension, the rate of isometric tension development, and the maximal rates of isometric and isotonic relaxation were significantly reduced in Hyp. Load-sensitive relaxation were significantly reduced in Hyp. Load-sensitive relaxation quantified by the ratio of a rapid loading to unloading force step in isotonically contracting papillary muscle was reduced 50% in Hyp muscles. Maximum activity of SR Ca(2+)-adenosinetriphosphatase (ATPase) measured under optimal conditions (37 degrees C; saturating Ca2+) was unaltered, but at low free Ca2+ concentrations (0.65 microM), it was decreased by 43% of the Sham response. Bivariate regression analysis revealed a significant (r = 0.84; P = 0.009) relationship between the decrease in SR Ca(2+)-ATPase activity and the loss of load-sensitive relaxation after aortic coarctation. Stimulation of the SR Ca(2+)-ATPase by the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent protein kinase resulted in a 2.6-fold increase for Sham but only a 1.6-fold increase for Hyp. Semiquantitative Western blot radioimmunoassays revealed that the changes in SR Ca(2+)-ATPase activity were not due to decreases in the content of the Ca(2+)-ATPase protein or phospholamban. Our data directly implicate a role for decreased SR function in attenuated load sensitivity. A purposeful downregulation of SR Ca2+ uptake likely results from a qualitative rather than a quantitative change in the ATPase and possibly one of its key regulators, phospholamban.

Effects of prior exercise and a low-carbohydrate diet on muscle sarcoplasmic reticulum function during cycling in women

2006 ◽  
Vol 101 (3) ◽  
pp. 695-706 ◽  
Author(s):  
T. A. Duhamel ◽  
H. J. Green ◽  
J. G. Perco ◽  
J. Ouyang
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Atpase Activity ◽  
Vastus Lateralis ◽  
Phase 1 ◽  
Vastus Lateralis Muscle ◽  
Low Carbohydrate Diet ◽  
Hill Slope ◽  
Low Carbohydrate ◽  
Exercise Induced

The effects of exercise and diet on sarcoplasmic reticulum Ca2+-cycling properties in female vastus lateralis muscle were investigated in two groups of women following four different conditions. The conditions were 4 days of a low-carbohydrate (Lo CHO) and glycogen-depleting exercise plus a Lo CHO diet (Ex + Lo CHO) ( experiment 2) and 4 days of normal CHO (Norm CHO) and glycogen-depleting exercise plus Norm CHO (Ex + Norm CHO) ( experiment 1). Peak aerobic power (V̇o2peak) was 38.1 ± 1.4 (SE); n = 9 and 35.6 ± 1.4 ml·kg−1·min−1; n = 9, respectively. Sarcoplasmic reticulum properties measured in vitro in homogenates (μmol·g protein−1·min−1) indicated exercise-induced reductions ( P < 0.05) in maximal Ca2+-ATPase activity (0 > 30, 60 min > fatigue), Ca2+ uptake (0 > 30 > 60 min, fatigue), and Ca2+ release, both phase 1 (0, 30 > 60 min, fatigue) and phase 2 (0 > 30, 60 min, fatigue; 30 min > fatigue) in Norm CHO. Exercise was without effect in altering the Hill slope ( nH), defined as the slope of relationship between Ca2+-ATPase activity and Ca2+ concentration. No differences were observed between Norm CHO and Ex+Norm CHO. Compared with Norm CHO, Lo CHO resulted in a lower ( P < 0.05) Ca2+ uptake, phase 1 Ca2+ release (30 min), and nH. Ex + Lo CHO resulted in a greater ( P < 0.05) Ca2+ uptake and nH compared with Lo CHO. The results demonstrate that Lo CHO alone can disrupt SR Ca2+ cycling and that, with the exception of Ca2+ release, a glycogen-depleting session of exercise before Lo CHO can reverse the effects.

Exercise prevents diabetes-induced impairment in superficial buffer barrier in porcine coronary smooth muscle

2004 ◽  
Vol 96 (3) ◽  
pp. 1069-1079 ◽  
Author(s):  
C. A. Witczak ◽  
M. Sturek
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Atpase Activity ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Diabetic Dyslipidemia ◽  
Coronary Smooth Muscle ◽  
Treatment Groups ◽  
Analysis Techniques ◽  
Intracellular Ca

In healthy coronary smooth muscle cells, the superficial sarcoplasmic reticulum (SR) buffers rise in intracellular Ca2+ levels. In diabetic dyslipidemia, basal Ca2+ levels are increased, yet Ca2+ influx is decreased and SR Ca2+ uptake is increased. Exercise prevents diabetic dyslipidemia-induced increases in basal Ca2+ levels and decreases in Ca2+ influx. We tested the hypothesis that diabetic dyslipidemia impairs Ca2+ extrusion via a decrease in superficial SR and that exercise will prevent these losses. Male Yucatan swine were maintained in four treatment groups: control, hyperlipidemic, diabetic dyslipidemic, and diabetic dyslipidemic plus aerobically exercise trained. Intracellular Ca2+ levels were measured during depolarization-induced Ca2+ influx and caffeine-induced SR Ca2+ release. Na+/Ca2+ exchanger and plasmalemmal Ca2+-ATPase activity were assessed by inhibition with low extracellular Na+ and 5,6-carboxyeosin, respectively. Superficial SR was quantified using the internal membrane dye 3,3′-dihexyloxacarbocyanine iodide (DiOC6) and novel analysis techniques. We found that, in diabetic dyslipidemia, Ca2+ extrusion was impaired and superficial SR was decreased. Exercise prevented the diabetic dyslipidemia-induced decrease in superficial SR and restored plasmalemmal Ca2+ extrusion. On the basis of these results, we conclude exercise attenuates the diabetic dyslipidemia-induced impairment in intracellular Ca2+ regulation.

scholarly journals Living myocardial slices: a novel multicellular model for cardiac translational research

2019 ◽  
Vol 41 (25) ◽  
pp. 2405-2408 ◽  
Author(s):  
Filippo Perbellini ◽  
Thomas Thum
Keyword(s):  
Translational Research ◽  
Cardiac Tissue ◽  
Heart Function ◽  
Cell Types ◽  
Human Model ◽  
Mechanical Stimuli ◽  
Cardiovascular Research ◽  
Functional Changes

Abstract Heart function relies on the interplay of several specialized cell types and a precisely regulated network of chemical and mechanical stimuli. Over the last few decades, this complexity has often been undervalued and progress in translational cardiovascular research has been significantly hindered by the lack of appropriate research models. The data collected are often oversimplified and these make the translation of results from the laboratory to clinical trials challenging and occasionally misleading. Living myocardial slices are ultrathin (100–400μm) sections of living cardiac tissue that maintain the native multicellularity, architecture, and structure of the heart and can provide information at a cellular/subcellular level. They overcome most of the limitations that affect other in vitro models and they can be prepared from human specimens, proving a clinically relevant multicellular human model for translational cardiovascular research. The publication of a reproducible protocol, and the rapid progress in methodological and technological discoveries which prevent significant structural and functional changes associated with chronic in vitro culture, has overcome the last barrier for the in vitro use of this human multicellular preparations. This technology can bridge the gap between in vitro and in vivo human studies and has the potential to revolutionize translational research approaches.

Effects of prolonged low frequency stimulation on skeletal muscle sarcoplasmic reticulum

1995 ◽  
Vol 73 (8) ◽  
pp. 1154-1164 ◽  
Author(s):  
E. R. Chin ◽  
H. J Green ◽  
F. Grange ◽  
J. Dossett-Mercer ◽  
P. J. O'Brien
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Atpase Activity ◽  
Metabolic Response ◽  
Contractile Activity ◽  
Creatine Phosphate ◽  
Energy Status ◽  
Muscle Lactate ◽  
Muscle Energy

The role of prolonged electrical stimulation on sarcoplasmic reticulum (SR) Ca2+sequestration measured in vitro and muscle energy status in fast white and red skeletal muscle was investigated. Fatigue was induced by 90 min intermittent 10-Hz stimulation of rat gastrocnemius muscle, which led to reductions (p < 0.05) in ATP, creatine phosphate, and glycogen of 16, 55, and 49%, respectively, compared with non-stimulated muscle. Stimulation also resulted in increases (p < 0.05) in muscle lactate, creatine, Pi, total ADP, total AMP, IMP, and inosine. Calculated free ADP (ADPf) and free AMP (AMPf) were elevated 3- and 15-fold, respectively. No differences were found in the metabolic response between tissues obtained from the white (WG) and red (RG) regions of the gastrocnemius. No significant reductions in SR Ca2+ATPase activity were observed in homogenate (HOM) or a crude SR fraction (CM) from WG or RG muscle following exercise. Maximum Ca2+uptake in HOM and CM preparations was similar in control (C) and stimulated (St) muscles. However, Ca2+uptake at 400 nM free Ca2+was significantly reduced in CM from RG (0.108 ± 0.04 to 0.076 ± 0.02 μmol∙mg−1protein∙min−1in RG–C and RG–St, respectively). Collectively, these data suggest that reductions in muscle energy status are dissociated from changes in SR Ca2+ATPase activity in vitro but are related to Ca2+uptake at physiological free [Ca2+] in fractionated SR from highly oxidative muscle. Dissociation of SR Ca2+ATPase activity from Ca2+uptake may reflect differences in the mechanisms evaluated by these techniques.Key words: sarcoplasmic reticulum, contractile activity, Ca2+sequestration, energy status, red and white gastrocnemius.

scholarly journals 4-[1-ethyl-1-methylhexy]-phenol Induces Apoptosis and Interrupts Ca2+ Homeostasis via ROS Pathway in Sertoli TM4 cells

2021 ◽  
Author(s):  
Xiaozhen Liu ◽  
Fuxiang Li ◽  
Zhaoliang Zhu ◽  
Gaoyi Peng ◽  
Danfei Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Atpase Activity ◽  
Chain Structure ◽  
Side Chain ◽  
Ros Generation ◽  
Intracellular Ca ◽  
Ros Scavenger ◽  
Induced Apoptosis ◽  
The Impact

Abstract Biological effect of an individual nonylphenol (NP) isomer extremely relies upon the side chain structure. This research was designed to evaluate the impact of NP isomer, 4-[1-ethyl-1-methylhexy]-phenol (NP65), on Sertoli cells in vitro. Sertoli TM4 cells were exposed to various concentration (0, 0.1, 1, 10, or 20 μM) of NP65 for 24 h, and the outcomes indicated that treatment of NP65 induced reactive oxygen species (ROS) generation, oxidative stress as well as apoptosis for Sertoli TM4 cells. In addition, it was found that NP65 exposure affected homeostasis of Ca2+ in Sertoli TM4 cells by increasing cytoplasm [Ca2+]i, inhibiting Ca2+-ATPase activity and decreasing cAMP concentration. Pretreatment with ROS scavenger, N-acetylcysteine (NAC), attenuated NP65-induced oxidative stress as well as apoptosis for TM4 cells. Furthermore, NAC blocked NP65-induced disorders of Ca2+ homeostasis by attenuating the growth of intracellular [Ca2+]i and the inhibition of Ca2+-ATPase and cAMP activities. Thus, we have demonstrated that NP65 induced apoptosis as well as acted as a potent inhibitor of Ca2+-ATPase activity and resulted in disorder of Ca2+ homeostasis in Sertoli TM4 cells, ROS participated in the process. Our results supported the view that oxidative stress acted an essential role within the development of apoptosis and Ca2+ overload in TM4 cells as a consequence of NP65 stimulation.

Preservation of sarcoplasmic reticulum Ca2+-sequestering function in homogenates of different fibre type composition following sprint activity

1994 ◽  
Vol 72 (10) ◽  
pp. 1231-1237 ◽  
Author(s):  
J. Dossett-Mercer ◽  
H. J. Green ◽  
E. Chin ◽  
F. Grange
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Atpase Activity ◽  
Dry Weight ◽  
Muscle Fibre Types ◽  
Glycogen Depletion ◽  
Fibre Type Composition ◽  
Fibre Composition ◽  
Type Composition ◽  
Male Wistar Rats

To examine the effect of exercise on sarcoplasmic reticulum function in muscle tissue of different fibre composition, adult male Wistar rats weighing 388 ± 23 g (x ± SE) ran intermittently on a treadmill until fatigue. Fatigue was induced by 15–20 min of running performed at 52 m/min on an 8° incline in periods of 2.5 min of exercise separated by 2 min of recovery. Analysis of sarcoplasmic reticulum Ca2+ ATPase activity determined in homogenates indicated no difference (p > 0.05) between age-matched control and exercised tissue for the soleus (SOL; 0.121 ± 0.012 vs. 0.156 ± 0.018 μmol∙mg−1 protein∙min−1), red gastrocnemius (RG; 0.381 ± 0.022 vs. 0.354 ± 0.022), or white gastrocnemius (WG; 0.526 ± 0.05 vs. 0.471 ± 0.031). Similarly, both total ATPase and Mg2+ ATPase activities were unaffected by the exercise in any of the tissues examined. Exercise also failed to alter sarcoplasmic reticulum Ca2+ uptake in homogenates of the SOL (1.43 ± 0.15 vs. 1.38 ± 0.19 nmol∙mg−1 protein∙min−1), RG (3.74 ± 0.29 vs. 3.59 ± 0.24), and WG (5.98 ± 0.48 vs. 5.41 ± 0.50). At fatigue, glycogen depletion was similar in all tissue types and amounted to 65.1% in the SOL (172 ± 9 vs. 60 ± 16 mmol∙glucosyl units−1∙kg−1 dry weight), 74.4% in RG (164 ± 8 vs. 42 ± 6), and 79% in the WG (167 ± 9 vs. 35 ± 9). It is concluded that exercise by itself does not alter sarcoplasmic reticulum Ca2+-sequestering function in tissues of primarily different fibre composition when determined in homogenates in vitro. The integrity of sarcoplasmic reticulum function is preserved despite an apparent extensive recruitment of all tissue types during the exercise.Key words: sarcoplasmic reticulum function, Ca2+ uptake, Ca2+ ATPase activity, muscle fibre types.

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