Importance of the sarcoplasmic reticulum and adrenergic stimulation on the cardiac contractility of the neotropical teleost Synbranchus marmoratus under different thermal conditions

2007 ◽  
Vol 177 (7) ◽  
pp. 713-721 ◽  
Author(s):  
Matheus L. Rocha ◽  
Francisco T. Rantin ◽  
Ana L. Kalinin
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Contractility ◽  
Thermal Conditions ◽  
Adrenergic Stimulation

scholarly journals Spontaneous calcium release in tissue from the failing canine heart

2009 ◽  
Vol 297 (4) ◽  
pp. H1235-H1242 ◽  
Author(s):  
Gregory S. Hoeker ◽  
Rodolphe P. Katra ◽  
Lance D. Wilson ◽  
Bradley N. Plummer ◽  
Kenneth R. Laurita
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Tissue Level ◽  
Calcium Handling ◽  
Canine Heart ◽  
Myocardial Cells ◽  
Spontaneous Release ◽  
Adrenergic Stimulation ◽  
Electrical Instability ◽  
Delayed Afterdepolarization

Abnormalities in calcium handling have been implicated as a significant source of electrical instability in heart failure (HF). While these abnormalities have been investigated extensively in isolated myocytes, how they manifest at the tissue level and trigger arrhythmias is not clear. We hypothesize that in HF, triggered activity (TA) is due to spontaneous calcium release from the sarcoplasmic reticulum that occurs in an aggregate of myocardial cells (an SRC) and that peak SCR amplitude is what determines whether TA will occur. Calcium and voltage optical mapping was performed in ventricular wedge preparations from canines with and without tachycardia-induced HF. In HF, steady-state calcium transients have reduced amplitude [135 vs. 170 ratiometric units (RU), P < 0.05] and increased duration (252 vs. 229 s, P < 0.05) compared with those of normal. Under control conditions and during β-adrenergic stimulation, TA was more frequent in HF (53% and 93%, respectively) compared with normal (0% and 55%, respectively, P < 0.025). The mechanism of arrhythmias was SCRs, leading to delayed afterdepolarization-mediated triggered beats. Interestingly, the rate of SCR rise was greater for events that triggered a beat (0.41 RU/ms) compared with those that did not (0.18 RU/ms, P < 0.001). In contrast, there was no difference in SCR amplitude between the two groups. In conclusion, TA in HF tissue is associated with abnormal calcium regulation and mediated by the spontaneous release of calcium from the sarcoplasmic reticulum in aggregates of myocardial cells (i.e., an SCR), but importantly, it is the rate of SCR rise rather than amplitude that was associated with TA.

Relation between contractile function and regulatory cardiac proteins in hypertrophied hearts

1996 ◽  
Vol 270 (6) ◽  
pp. H2021-H2028 ◽  
Author(s):  
B. Stein ◽  
S. Bartel ◽  
U. Kirchhefer ◽  
S. Kokott ◽  
E. G. Krause ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Troponin I ◽  
Contractile Function ◽  
Papillary Muscles ◽  
Camp Accumulation ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
C Protein ◽  
Camp Formation ◽  
Phosphate Incorporation

The aim of this study was to examine the mechanism(s) underlying the reduced isoproterenol-induced positive inotropic and lusitropic effects in hypertrophied hearts. Chronic beta-adrenergic stimulation (2.4 mg isoproterenol.kg-1. day-1 for 4 days) induced cardiac hypertrophy by 33 +/- 2% in rats. A parallel downregulation of phospholamban (PLB) and sarcoplasmic reticulum Ca2(+)-ATPase (SERCA2) protein expression by 49 and 40%, respectively, was observed, whereas troponin I (TNI) and C protein remained unchanged. In papillary muscles from chronically beta-adrenergically stimulated rats, the isoproterenol-induced positive inotropic and lusitropic effects, as well as adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, were attenuated compared with those in control animals. Acute exposure to isoproterenol induced phosphate incorporation into PLB, TNI, and C protein of 48 +/- 4.6, 55 +/- 5.0, and 27 +/- 4.9 pmol/mg homogenate protein, respectively, in control animals. In the hypertrophied hearts, phosphate incorporation into PLB was reduced by 76%, whereas phosphate incorporation into TNI or C protein remained unchanged. In conclusion, chronic beta-adrenergic stimulation reduced the isoproterenol-stimulated positive inotropic and lusitropic effects in papillary muscles, which were accompanied by 1) diminished cAMP formation, 2) attenuation of cAMP-mediated PLB phosphorylation, and 3) downregulation of PLB and SERCA2 protein.

Defibrillation depresses heart sarcoplasmic reticulum calcium pump: a mechanism of postshock dysfunction

1998 ◽  
Vol 274 (1) ◽  
pp. H98-H105 ◽  
Author(s):  
Douglas L. Jones ◽  
Njanoor Narayanan
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Atp Hydrolysis ◽  
Myocardial Dysfunction ◽  
Cardiac Contractility ◽  
Membrane Vesicles ◽  
Intracellular Ca ◽  
Current Densities ◽  
Langendorff Hearts ◽  
Pumping Function ◽  
Sarcoplasmic Reticulum Calcium

Presently, the only therapy for ventricular fibrillation is delivery of high-voltage shocks. Despite “successful defibrillation,” patients may have poor cardiac contractility, the mechanisms of which are unknown. Intracellular Ca2+ handling by the sarcoplasmic reticulum (SR) plays a major role in contractility. We tested the hypothesis that defibrillation shocks interfere with Ca2+ transport function of cardiac SR. Rats anesthetized with pentobarbital sodium had bilateral electrodes implanted subcutaneously for transthoracic shocks. A series of 10 shocks, 10 s apart, at 0–250 V was delivered from a trapezoidal defibrillator. The hearts were rapidly removed, SR-enriched membrane vesicles were isolated, and ATP-dependent Ca2+ uptake and Ca2+-stimulated ATP hydrolysis were determined. There was a marked, shock-related decline in Ca2+ uptake, whereas adenosinetriphosphatase activity remained unaltered. The polypeptide compositions were similar in control and shocked SR. In Langendorff hearts, shocks also decreased contractility and slowed relaxation. These data indicate that shocks with current densities similar to defibrillation depress Ca2+-pumping function of cardiac SR because of uncoupling of ATP hydrolysis and Ca2+ transport. Shock-induced impairment of Ca2+ pump function may underlie postshock myocardial dysfunction.

scholarly journals Phosphorylation of the ryanodine receptor 2 at serine 2030 is required for a complete β-adrenergic response

2018 ◽  
Vol 151 (2) ◽  
pp. 131-145 ◽  
Author(s):  
Duilio M. Potenza ◽  
Radoslav Janicek ◽  
Miguel Fernandez-Tenorio ◽  
Emmanuel Camors ◽  
Roberto Ramos-Mondragón ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Cardiac Contractility ◽  
Phosphorylation Site ◽  
Adrenergic Stimulation ◽  
Permeabilized Cells ◽  
Whole Cell Patch Clamp ◽  
Adrenergic Response ◽  
Pump Activity ◽  
Ryr2 Channel ◽  
A Site

During physical exercise or stress, the sympathetic system stimulates cardiac contractility via β-adrenergic receptor (β-AR) activation, resulting in protein kinase A (PKA)–mediated phosphorylation of the cardiac ryanodine receptor RyR2. PKA-dependent “hyperphosphorylation” of the RyR2 channel has been proposed as a major impairment that contributes to progression of heart failure. However, the sites of PKA phosphorylation and their phosphorylation status in cardiac diseases are not well defined. Among the known RyR2 phosphorylation sites, serine 2030 (S2030) remains highly controversial as a site of functional impact. We examined the contribution of RyR2-S2030 to Ca2+ signaling and excitation–contraction coupling (ECC) in a transgenic mouse with an ablated RyR2-S2030 phosphorylation site (RyR2-S2030A+/+). We assessed ECC gain by using whole-cell patch–clamp recordings and confocal Ca2+ imaging during β-ARs stimulation with isoproterenol (Iso) and consistent SR Ca2+ loading and L-type Ca2+ current (ICa) triggering. Under these conditions, ECC gain is diminished in mutant compared with WT cardiomyocytes. Resting Ca2+ spark frequency (CaSpF) with Iso is also reduced by mutation of S2030. In permeabilized cells, when SR Ca2+ pump activity is kept constant (using 2D12 antibody against phospholamban), cAMP does not change CaSpF in S2030A+/+ myocytes. Using Ca2+ spark recovery analysis, we found that mutant RyR Ca2+ sensitivity is not enhanced by Iso application, contrary to WT RyRs. Furthermore, ablation of RyR2-S2030 prevents acceleration of Ca2+ waves and increases latency to the first spontaneous Ca2+ release after a train of stimulations during Iso treatment. Together, these results suggest that phosphorylation at S2030 may represent an important step in the modulation of RyR2 activity during β-adrenergic stimulation and a potential target for the development of new antiarrhythmic drugs.

scholarly journals ?-Adrenergic stimulation produces a decrease of cardiac contractility ex vivo in mice overexpressing the human ?-adrenergic receptor

2003 ◽  
Vol 59 (2) ◽  
pp. 288-296 ◽  
Author(s):  
G TAVERNIER ◽  
G TOUMANIANTZ ◽  
M ERFANIAN ◽  
M HEYMANN ◽  
K LAURENT ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Ex Vivo ◽  
Cardiac Contractility ◽  
Adrenergic Stimulation

Abstract 65: β-Adrenergic Signaling Promotes Survival and Proliferation of Mouse Cardiac Progenitor Cells Prior to Lineage Commitment

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Mohsin Khan ◽  
Sadia Mohsin ◽  
Daniele Avitabile ◽  
Jonathan Nguyen ◽  
Natalie Gude ◽  
...  
Keyword(s):  
Recovery Of Function ◽  
Cardiac Contractility ◽  
Stem Cell Marker ◽  
Adrenergic Blockade ◽  
Adrenergic Stimulation ◽  
Myocardial Repair ◽  
Akt Phosphorylation ◽  
Failing Heart

Rationale: Short term β-adrenergic stimulation promotes contractility in response to stress, but is ultimately detrimental in the failing heart due to accrual of cardiomyocyte death. Endogenous myocardial repair may partially offset cardiomyocyte losses, but consequences of long term β-adrenergic drive upon myocardial repair and regeneration are unknown. Objective: Modest recovery of cardiac contractility following long term β-adrenergic blockade in the clinical setting may depend, in part, upon restoration of endogenous repair therefore we sought to determine the relationship between β-adrenergic activity and regulation of cardiac progenitor cell (CPC) function and influence upon myocardial repair. Methods and results: Mouse and human CPCs express only β2 adrenergic receptor (β2-AR) in conjunction with stem cell marker c-kit. Activation of β2-AR signaling promotes proliferation associated with increased Akt phosphorylation, up-regulation of eNOS and cyclin D1, and decreased levels of GRK2. Conversely, silencing of β2-AR expression or treatment with β2-antagonist ICI 118, 551 impairs proliferation and survival. β1-AR expression in CPC is induced by differentiation stimuli, sensitizing CPC to isoproterenol-induced cell death that is abrogated by the β1-AR specific antagonist metoprolol. Efficacy of β1-AR blockade by metoprolol to increase CPC survival and proliferation was confirmed in vivo by adoptive transfer of CPC into failing mouse myocardium, concomitant with increased ejection fraction, fractional shortening and hemodynamic performance. Conclusions: β-adrenergic stimulation promotes expansion and survival of CPCs through β2-AR, but acquisition of β1-AR upon commitment to the myocyte lineage results in loss of early myocyte precursors and ineffective myocardial repair. Thus, β1-AR-specific blockade is likely to provide for enhanced CPC participation in recovery of function in the failing heart.

Modulation of mouse cardiac function in vivo by eNOS and ANP

2000 ◽  
Vol 278 (3) ◽  
pp. H971-H981 ◽  
Author(s):  
Robert Gyurko ◽  
Peter Kuhlencordt ◽  
Mark C. Fishman ◽  
Paul L. Huang
Keyword(s):  
Cardiac Function ◽  
Isolated Heart ◽  
Cardiac Contractility ◽  
Enos Gene ◽  
Wild Type ◽  
Adrenergic Stimulation ◽  
Microvascular Endothelium ◽  
Ventricular Relaxation ◽  
Nos Inhibitors

To study the role of endothelial nitric oxide synthase (eNOS) in cardiac function, we compared eNOS expression, contractility, and relaxation in the left ventricles of wild-type and eNOS-deficient mice. eNOS immunostaining is localized to the macro- and microvascular endothelium throughout the myocardium in wild-type mice and is absent in eNOS−/− mice. Whereas blood pressure is elevated in eNOS−/− mice, baseline cardiac contractility (dP/d t max) is similar in wild-type and eNOS−/− mice (9,673 ± 2,447 and 9,928 ± 1,566 mmHg/s, respectively). The β-adrenergic agonist isoproterenol (Iso) at doses of ≥1 ng causes enhanced increases in dP/d t max in eNOS−/− mice compared with wild-type controls in vivo ( P < 0.01) as well as in Langendorff isolated heart preparations ( P < 0.02). β-Adrenergic receptor binding (Bmax) is not significantly different in the two groups of animals (Bmax = 41.4 ± 9.4 and 36.1 ± 5.1 fmol/mg for wild-type and eNOS−/−). Iso-stimulated ventricular relaxation is also enhanced in the eNOS−/− mice, as measured by dP/d t min in the isolated heart. However, baseline ventricular relaxation is normal in eNOS−/− mice (τ = 5.2 ± 1.0 and 5.6 ± 1.5 ms for wild-type and eNOS−/−, respectively), whereas it is impaired in wild-type mice after NOS inhibition (τ = 8.3 ± 2.4 ms). cGMP levels in the left ventricle are unaffected by eNOS gene deletion (wild-type: 3.1 ± 0.8 pmol/mg, eNOS−/−: 3.1 ± 0.6 pmol/mg), leading us to examine the level of another physiological regulator of cGMP. Atrial natriuretic peptide (ANP) expression is markedly upregulated in the eNOS−/− mice, and exogenous ANP restores ventricular relaxation in wild-type mice treated with NOS inhibitors. These results suggest that eNOS attenuates both inotropic and lusitropic responses to β-adrenergic stimulation, and it also appears to regulate baseline ventricular relaxation in conjunction with ANP.

Adenosine inhibition of beta-adrenergic induced responses in aged hearts

1993 ◽  
Vol 265 (2) ◽  
pp. H494-H503 ◽  
Author(s):  
J. G. Dobson ◽  
R. A. Fenton
Keyword(s):  
Adenosine Deaminase ◽  
Glycogen Phosphorylase ◽  
Cardiac Contractility ◽  
Sprague Dawley ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Fischer 344 ◽  
Rat Hearts ◽  
Fischer 344 Rat ◽  
Glycogen Phosphorylase Activity

Because adenosine has an antiadrenergic action in the heart, young (3-4 mo) and aged (18-20 mo) adult Sprague-Dawley and Fischer 344 rat hearts were perfused to determine whether interstitial adenosine plays a role in the reduced metabolic and mechanical responsiveness of the aged heart to beta-adrenergic stimulation. Interstitial adenosine was approximately twofold greater in aged hearts compared with young adult hearts, and 10(-8) M isoproterenol (ISO) further increased these levels. ISO increased myocardial adenosine 3',5'-cyclic monophosphate content, glycogen phosphorylase activity, and cardiac contractility by 83, 150, and 130%, respectively, in young hearts but only increased these variables by 45, 74, and 61%, respectively, in aged hearts. Sulfophenyl-theophylline prevented the reduced ISO-induced responsiveness of the above variables in aged hearts. Exogenously administered adenosine deaminase eliminated the reduced ISO-induced contractile responsiveness in aged hearts. The apparent activities of 5'-nucleotidase and adenosine deaminase were not significantly different in ventricular samples from young and aged hearts. These results suggest that the elevated interstitial level of adenosine exerts a greater antiadrenergic effect in the aged heart, rendering it less responsive to beta-adrenergic stimulation. The increased interstitial level of adenosine in the aged heart does not appear to be due to a difference in the activities of either 5'-nucleotidase or adenosine deaminase.

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