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.

Prevention of endotoxin-induced sarcoplasmic reticulum calcium leak improves mitochondrial and myocardial dysfunction*

2008 ◽  
Vol 36 (9) ◽  
pp. 2590-2596 ◽  
Author(s):  
Sidi Mohammed Hassoun ◽  
Xavier Marechal ◽  
David Montaigne ◽  
Youcef Bouazza ◽  
Brigitte Decoster ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Myocardial Dysfunction ◽  
Sarcoplasmic Reticulum Calcium

Invariance of Stoichiometry of the Sarcoplasmic Reticulum Calcium Pump at Physiological Calcium Concentrations – a Reevaluation

1985 ◽  
Vol 40 (7-8) ◽  
pp. 571-575 ◽  
Author(s):  
Wilhelm Hasselbach ◽  
Andrea Migala
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Level ◽  
Calcium Concentration ◽  
Calcium Uptake ◽  
Atp Hydrolysis ◽  
Calcium Pump ◽  
Oxalate Precipitation ◽  
Sarcoplasmic Reticulum Calcium ◽  
Internal Calcium ◽  
External Calcium

Abstract The decline of the transport ratio of the sarcoplasmic calcium pump observed in a recent study (A. results from the retardation of calcium oxalate precipitation at low calcium/protein ratios. The prevailing high internal calcium level supports a rapid calcium backflux and a compensatory ATP hydrolysis during net calcium uptake which reduces the transport ratio. Yet, the determined calcium back­ flux does not fully account for the decline of the transport ratio. A supposed modulation of the stoichiometry of the pump by external calcium (0.1 μм) is at variance with results of previous studies showing a constant transport ratio of two in the same calcium concentration range.

scholarly journals Induced overexpression of phospholemman S68E mutant improves cardiac contractility and mortality after ischemia-reperfusion

2014 ◽  
Vol 306 (7) ◽  
pp. H1066-H1077 ◽  
Author(s):  
JuFang Wang ◽  
Jianliang Song ◽  
Erhe Gao ◽  
Xue-Qian Zhang ◽  
Tongda Gu ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ischemia Reperfusion ◽  
Cardiac Contractility ◽  
Left Ventricular ◽  
Wild Type ◽  
Protein Levels ◽  
Plasmic Reticulum ◽  
Intracellular Ca ◽  
Similar Survival

Phospholemman (PLM), when phosphorylated at Ser68, inhibits cardiac Na+/Ca2+ exchanger 1 (NCX1) and relieves its inhibition on Na+-K+-ATPase. We have engineered mice in which expression of the phosphomimetic PLM S68E mutant was induced when dietary doxycycline was removed at 5 wk. At 8–10 wk, compared with noninduced or wild-type hearts, S68E expression in induced hearts was ∼35–75% that of endogenous PLM, but protein levels of sarco(endo)plasmic reticulum Ca2+-ATPase, α1- and α2-subunits of Na+-K+-ATPase, α1c-subunit of L-type Ca2+ channel, and phosphorylated ryanodine receptor were unchanged. The NCX1 protein level was increased by ∼47% but the NCX1 current was depressed by ∼34% in induced hearts. Isoproterenol had no effect on NCX1 currents but stimulated Na+-K+-ATPase currents equally in induced and noninduced myocytes. At baseline, systolic intracellular Ca2+ concentrations ([Ca2+]i), sarcoplasmic reticulum Ca2+ contents, and [Ca2+]i transient and contraction amplitudes were similar between induced and noninduced myocytes. Isoproterenol stimulation resulted in much higher systolic [Ca2+]i, sarcoplasmic reticulum Ca2+ content, and [Ca2+]i transient and contraction amplitudes in induced myocytes. Echocardiography and in vivo close-chest catheterization demonstrated similar baseline myocardial function, but isoproterenol induced a significantly higher +dP/d t in induced compared with noninduced hearts. In contrast to the 50% mortality observed in mice constitutively overexpressing the S68E mutant, induced mice had similar survival as wild-type and noninduced mice. After ischemia-reperfusion, despite similar areas at risk and left ventricular infarct sizes, induced mice had significantly higher +dP/d t and −dP/d t and lower perioperative mortality compared with noninduced mice. We propose that phosphorylated PLM may be a novel therapeutic target in ischemic heart disease.

Correlation Between Functional Recovery From Ischemia and Sarcoplasmic Reticulum Calcium Content Measured by Electron Probe MicroAnalysis

1997 ◽  
Vol 3 (S2) ◽  
pp. 921-922
Author(s):  
L.S. Barrett ◽  
W.E. Sweet ◽  
C.S. Moravec
Keyword(s):  
Blood Flow ◽  
Sarcoplasmic Reticulum ◽  
Myocardial Ischemia ◽  
Functional Recovery ◽  
Electron Probe ◽  
Calcium Content ◽  
Normal Flow ◽  
Flow Conditions ◽  
Intracellular Ca ◽  
Sarcoplasmic Reticulum Calcium

Myocardial ischemia is defined as a cessation of blood flow to the heart, and reperfusion as a return to normal flow conditions following ischemia. It has been shown that contractility decreases immediately during ischemia and diastolic dysfunctiuon may persist during reperfusion. Changes in contractility can be directly attributed to intracellular Ca2+ handling, either by altering the myofilament sensitivity to calcium or by affecting Ca2+ cycling by the sarcoplasmic reticulum (SR). Previous studies have demonstrated that there are changes in intracellular Ca2+ cycling following ischemia and during reperfusion. The goals of the present study were: 1) to assess the effects of varying periods of ischemia on the size of the releasable (diastolic) SR Ca2+ store; 2) to determine whether changes in the size of the SR Ca2+ store are related to ischemia or reperfusion; 3) to correlate changes in the size of the SR Ca2+ store following ischemia with functional recovery of the heart.

scholarly journals Targeted Overexpression of Sarcolipin in the Mouse Heart Decreases Sarcoplasmic Reticulum Calcium Transport and Cardiac Contractility

2006 ◽  
Vol 281 (7) ◽  
pp. 3972-3979 ◽  
Author(s):  
Gopal J. Babu ◽  
Poornima Bhupathy ◽  
Natalia N. Petrashevskaya ◽  
Honglan Wang ◽  
Sripriya Raman ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Transport ◽  
Cardiac Contractility ◽  
Mouse Heart ◽  
Sarcoplasmic Reticulum Calcium

Targeted inhibition of sarcoplasmic reticulum CaMKII activity results in alterations of Ca2+ homeostasis and cardiac contractility

2006 ◽  
Vol 290 (2) ◽  
pp. H599-H606 ◽  
Author(s):  
Yong Ji ◽  
Wen Zhao ◽  
Bailing Li ◽  
Jaime Desantiago ◽  
Eckard Picht ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Cardiac Myocyte ◽  
Cardiac Contractility ◽  
Dependent Manner ◽  
Inhibitory Peptide ◽  
Intracellular Ca ◽  
Dependent Protein ◽  
Targeted Inhibition ◽  
Contraction And Relaxation

Transgenic (TG) mice expressing a Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitory peptide targeted to the cardiac myocyte longitudinal sarcoplasmic reticulum (LSR) display reduced phospholamban phosphorylation at Thr17 and develop dilated myopathy when stressed by gestation and parturition (Ji Y, Li B, Reed TD, Lorenz JN, Kaetzel MA, and Dedman JR. J Biol Chem 278: 25063–25071, 2003). In the present study, these animals (TG) are evaluated for the effect of inhibition of sarcoplasmic reticulum (SR) CaMKII activity on the contractile characteristics and Ca2+ cycling of myocytes. Analysis of isolated work-performing hearts demonstrated moderate decreases in the maximal rates of contraction and relaxation (±dP/d t) in TG mice. The response of the TG hearts to increases in load is reduced. The TG hearts respond to isoproterenol (Iso) in a dose-dependent manner; the contractile properties were reduced in parallel to wild-type hearts. Assessment of isolated cardiomyocytes from TG mice revealed 40–47% decrease in the maximal rates of myocyte shortening and relengthening under both basal and Iso-stimulated conditions. Although twitch Ca2+ transient amplitudes were not significantly altered, the rate of twitch intracellular Ca2+ concentration decline was reduced by ∼47% in TG myocytes, indicating decreased SR Ca2+ uptake function. Caffeine-induced Ca2+ transients indicated unaltered SR Ca2+ content and Na+/Ca2+ exchange function. Phosphorylation assays revealed an ∼30% decrease in the phosphorylation of ryanodine receptor Ser2809. Iso stimulation increased the phosphorylation of both phospholamban Ser16 and the ryanodine receptor Ser2809 but not phospholamban Thr17 in TG mice. This study demonstrates that inhibition of SR CaMKII activity at the LSR results in alterations in cardiac contractility and Ca2+ handling in TG hearts.

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