ATP-dependent effects of halothane on SR Ca regulation in permeabilized atrial myocytes

Yang, Zhaokang; Harrison, Simon; Steele, Derek S.

doi:10.1016/j.cardiores.2004.09.008

Cited by 8 publications

(8 citation statements)

References 31 publications

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“…10 min before the end of the incubation, cells were loaded with fura-2 [17] or fluo-3 [19]. Cells were centrifuged as before, the supernatant removed and the pellet resuspended in incubation solution.…”

Section: Methodsmentioning

confidence: 99%

TNF-α and IL-1β increase Ca2+ leak from the sarcoplasmic reticulum and susceptibility to arrhythmia in rat ventricular myocytes

Duncan¹,

Yang²,

Hopkins³

et al. 2010

Cell Calcium

138

111

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Sepsis is associated with ventricular dysfunction and increased incidence of atrial and ventricular arrhythmia however the underlying pro-arrhythmic mechanisms are unknown. Serum levels of tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are elevated during sepsis and affect Ca2+ regulation. We investigated whether pro-inflammatory cytokines disrupt cellular Ca2+ cycling leading to reduced contractility, but also increase the probability of pro-arrhythmic spontaneous Ca2+ release from the sarcoplasmic reticulum (SR). Isolated rat ventricular myocytes were exposed to TNF-α (0.05 ng ml−1) and IL-1β (2 ng ml−1) for 3 hr and then loaded with fura-2 or fluo-3 to record the intracellular Ca2+ concentration ([Ca2+]i). Cytokine treatment decreased the amplitude of the spatially averaged Ca2+ transient and the associated contraction, induced asynchronous Ca2+ release during electrical stimulation, increased the frequency of localized Ca2+ release events, decreased the SR Ca2+ content and increased the frequency of spontaneous Ca2+ waves at any given cytoplasmic Ca2+. These data suggest that TNF-α and IL-1β increase the SR Ca2+ leak from the SR, which contributes to the depressed Ca2+ transient and contractility. Increased susceptibility to spontaneous SR Ca2+ release may contribute to arrhythmias in sepsis as the resulting Ca2+ extrusion via NCX is electrogenic, leading to cell depolarisation.

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Section: Methodsmentioning

confidence: 99%

TNF-α and IL-1β increase Ca2+ leak from the sarcoplasmic reticulum and susceptibility to arrhythmia in rat ventricular myocytes

Duncan¹,

Yang²,

Hopkins³

et al. 2010

Cell Calcium

138

111

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“…In septic cardiomyopathy, the systolic Ca 2ϩ transient is decreased, which is associated with a decrease in the SR Ca 2ϩ content (4,10,11). It is well established that the SR Ca 2ϩ content is finely tuned by the SR Ca 2ϩ recycling through SR Ca 2ϩ -ATPase and diastolic SR Ca 2ϩ release, also called SR Ca 2ϩ leak, through the RyRs (9,12). In a number of reports, the reduced SR Ca 2ϩ content has been attributed to the depressed SR Ca 2ϩ -ATPase function (12)(13)(14).…”

Section: Studies Suggest the Potential Role Of A Sarcoplasmic Reticulmentioning

confidence: 99%

“…It is well established that the SR Ca 2ϩ content is finely tuned by the SR Ca 2ϩ recycling through SR Ca 2ϩ -ATPase and diastolic SR Ca 2ϩ release, also called SR Ca 2ϩ leak, through the RyRs (9,12). In a number of reports, the reduced SR Ca 2ϩ content has been attributed to the depressed SR Ca 2ϩ -ATPase function (12)(13)(14). Another potential cause of the reduced SR Ca 2ϩ content is increased diastolic SR Ca 2ϩ leak.…”

Section: Studies Suggest the Potential Role Of A Sarcoplasmic Reticulmentioning

confidence: 99%

Toll-like receptor 4–induced ryanodine receptor 2 oxidation and sarcoplasmic reticulum Ca2+ leakage promote cardiac contractile dysfunction in sepsis

Yang

Zhang

Jiang

et al. 2018

Journal of Biological Chemistry

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Studies suggest the potential role of a sarcoplasmic reticulum (SR) Ca leak in cardiac contractile dysfunction in sepsis. However, direct supporting evidence is lacking, and the mechanisms underlying this SR leak are poorly understood. Here, we investigated the changes in cardiac Ca handling and contraction in LPS-treated rat cardiomyocytes and a mouse model of polymicrobial sepsis produced by cecal ligation and puncture (CLP). LPS decreased the systolic Ca transient and myocyte contraction as well as SR Ca content. Meanwhile, LPS increased Ca spark-mediated SR Ca leak. Preventing the SR leak with ryanodine receptor (RyR) blocker tetracaine restored SR load and increased myocyte contraction. Similar alterations in Ca handling were observed in cardiomyocytes from CLP mice. Treatment with JTV-519, an anti-SR leak drug, restored Ca handling and improved cardiac function. In the LPS-treated cardiomyocytes, mitochondrial reactive oxygen species and oxidative stress in RyR2 were increased, whereas the levels of the RyR2-associated FK506-binding protein 1B (FKBP12.6) were decreased. The Toll-like receptor 4 (TLR4)-specific inhibitor TAK-242 reduced the oxidative stress in LPS-treated cells, decreased the SR leak, and normalized Ca handling and myocyte contraction. Consistently, TLR4 deletion significantly improved cardiac function and corrected abnormal Ca handling in the CLP mice. This study provides evidence for the critical role of the SR Ca leak in the development of septic cardiomyopathy and highlights the therapeutic potential of JTV-519 by preventing SR leak. Furthermore, it reveals that TLR4 activation-induced mitochondrial reactive oxygen species production and the resulting oxidative stress in RyR2 contribute to the SR Ca leak.

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“…The relevance of its post‐ischaemic effect has been confirmed using an in vivo model, which was independent of the haemodynamic effect of halothane ( Schlack et al , 1997 ). The link to intracellular Ca 2+ mobilization has been recently highlighted by data suggesting that at low ATP levels the ryanodine receptor sensitivity increases in the presence of halothane ( Yang et al , 2005 ). Like other volatile anaesthetics, halothane has also been shown to induce preconditioning ( Piriou et al , 2002 ) and to reduce post‐ischaemic adhesion of neutrophils in the coronary system ( Kowalski et al , 1997 ).…”

Section: Anaesthetics As Cardioprotective Agentsmentioning

confidence: 99%

Inflammatory response and cardioprotection during open‐heart surgery: the importance of anaesthetics

Suleiman

Zacharowski

Angelini

2008

British J Pharmacology

137

108

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Open-heart surgery triggers an inflammatory response that is largely the result of surgical trauma, cardiopulmonary bypass, and organ reperfusion injury (e.g. heart). The heart sustains injury triggered by ischaemia and reperfusion and also as a result of the effects of systemic inflammatory mediators. In addition, the heart itself is a source of inflammatory mediators and reactive oxygen species that are likely to contribute to the impairment of cardiac pump function. Formulating strategies to protect the heart during open heart surgery by attenuating reperfusion injury and systemic inflammatory response is essential to reduce morbidity. Although many anaesthetic drugs have cardioprotective actions, the diversity of the proposed mechanisms for protection (e.g. attenuating Ca 2 þ overload, anti-inflammatory and antioxidant effects, pre-and post-conditioning-like protection) may have contributed to the slow adoption of anaesthetics as cardioprotective agents during open heart surgery. Clinical trials have suggested at least some cardioprotective effects of volatile anaesthetics. Whether these benefits are relevant in terms of morbidity and mortality is unclear and needs further investigation. This review describes the main mediators of myocardial injury during open heart surgery, explores available evidence of anaesthetics induced cardioprotection and addresses the efforts made to translate bench work into clinical practice.

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ATP-dependent effects of halothane on SR Ca regulation in permeabilized atrial myocytes

Cited by 8 publications

References 31 publications

TNF-α and IL-1β increase Ca2+ leak from the sarcoplasmic reticulum and susceptibility to arrhythmia in rat ventricular myocytes

TNF-α and IL-1β increase Ca2+ leak from the sarcoplasmic reticulum and susceptibility to arrhythmia in rat ventricular myocytes

Toll-like receptor 4–induced ryanodine receptor 2 oxidation and sarcoplasmic reticulum Ca2+ leakage promote cardiac contractile dysfunction in sepsis

Inflammatory response and cardioprotection during open‐heart surgery: the importance of anaesthetics

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