Biphasic modulation of ryanodine binding to sarcoplasmic reticulum vesicles of skeletal muscle by Zn2+ ions

Xia, Ruo Hong; Cheng, Xiaoyang; Wang, Hui; Chen, Ke Ying; Qin, Wei; Zhang, Xiao Hui; Zhu, Pei Hong

doi:10.1042/bj3450279

Cited by 8 publications

(5 citation statements)

References 17 publications

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“…In addition, our present work demonstrated, for the first time, that an increase in [Zn 2+ ] i is associated with hyperphosphorylation of the RyR2 in a concentration-dependent manner, at most via phosphorylation of both PKA and CamKII under acute zinc-inophore ZnPT exposure rather than a direct hyperphosphorylaion of RyR2 with increased [Zn 2+ ] i . This hypothesis depending on our observations is further supported with the data on multiple functional effects of [Zn 2+ ] i on CaMKII and modulation of RyR1 binding to SR vesicles in skeletal muscle biphasically [48], [49]. Indeed, it is well-accepted that [Zn 2+ ] i level plays critical roles in the redox signaling pathway and maintaining the normal structure and physiology of various cell types [62].…”

Section: Discussionsupporting

confidence: 90%

“…In addition, it has been shown that Zn 2+ has multiple functional effects on Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) [48], [49] while divalent metal ions influence catalysis and active-site accessibility in the cAMP-dependent protein kinase [50]. In order to demonstrate possibility of higher phosphorylation levels of two different kinases (PKA and CaMKII) with increased intracellular Zn 2+ , which are responsible from hyperphosphorylation of RyR2 under pathological conditions, rather than a direct hyperphosphorylated-RyR2 with Zn 2+ , in another set of experiments, we measured the phosphorylation levels of both PKA and CaMKII (with respect to their protein levels) with ZnPT exposures, under in vitro conditions.…”

Section: Resultsmentioning

confidence: 99%

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ß-Blocker Timolol Prevents Arrhythmogenic Ca2+ Release and Normalizes Ca2+ and Zn2+ Dyshomeostasis in Hyperglycemic Rat Heart

et al. 2013

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Defective cardiac mechanical activity in diabetes results from alterations in intracellular Ca2+ handling, in part, due to increased oxidative stress. Beta-blockers demonstrate marked beneficial effects in heart dysfunction with scavenging free radicals and/or acting as an antioxidant. The aim of this study was to address how β-blocker timolol-treatment of diabetic rats exerts cardioprotection. Timolol-treatment (12-week), one-week following diabetes induction, prevented diabetes-induced depressed left ventricular basal contractile activity, prolonged cellular electrical activity, and attenuated the increase in isolated-cardiomyocyte size without hyperglycemic effect. Both in vivo and in vitro timolol-treatment of diabetic cardiomyocytes prevented the altered kinetic parameters of Ca2+ transients and reduced Ca2+ loading of sarcoplasmic reticulum (SR), basal intracellular free Ca2+ and Zn2+ ([Ca2+]i and [Zn2+]i), and spatio-temporal properties of the Ca2+ sparks, significantly. Timolol also antagonized hyperphosphorylation of cardiac ryanodine receptor (RyR2), and significantly restored depleted protein levels of both RyR2 and calstabin2. Western blot analysis demonstrated that timolol-treatment also significantly normalized depressed levels of some [Ca2+]i-handling regulators, such as Na+/Ca2+ exchanger (NCX) and phospho-phospholamban (pPLN) to PLN ratio. Incubation of diabetic cardiomyocytes with 4-mM glutathione exerted similar beneficial effects on RyR2-macromolecular complex and basal levels of both [Ca2+]i and [Zn2+]i, increased intracellular Zn2+ hyperphosphorylated RyR2 in a concentration-dependent manner. Timolol also led to a balanced oxidant/antioxidant level in both heart and circulation and prevented altered cellular redox state of the heart. We thus report, for the first time, that the preventing effect of timolol, directly targeting heart, seems to be associated with a normalization of macromolecular complex of RyR2 and some Ca2+ handling regulators, and prevention of Ca2+ leak, and thereby normalization of both [Ca2+]i and [Zn2+]i homeostasis in diabetic rat heart, at least in part by controlling the cellular redox status of hyperglycemic cardiomyocytes.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

ß-Blocker Timolol Prevents Arrhythmogenic Ca2+ Release and Normalizes Ca2+ and Zn2+ Dyshomeostasis in Hyperglycemic Rat Heart

et al. 2013

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“…Mg 2+ , Zn 2+ , NO, and ATP are known modulators of the RyR function (Xia et al. ; Lanner et al. ; Suhr et al.…”

Section: Discussionmentioning

confidence: 99%

In vivo Ca²⁺ dynamics induced by Ca²⁺ injection in individual rat skeletal muscle fibers

Wakizaka

Eshima

Tanaka

et al. 2017

Physiological Reports

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In contrast to cardiomyocytes, store overload‐induced calcium ion (Ca2+) release (SOICR) is not considered to constitute a primary Ca2+ releasing system from the sarcoplasmic reticulum (SR) in skeletal muscle myocytes. In the latter, voltage‐induced Ca2+ release (VICR) is regarded as the dominant mechanism facilitating contractions. Any role of the SOICR in the regulation of cytoplasmic Ca2+ concentration ([Ca2+]i) and its dynamics in skeletal muscle in vivo remains poorly understood. By means of in vivo single fiber Ca2+ microinjections combined with bioimaging techniques, we tested the hypothesis that the [Ca2+]i dynamics following Ca2+ injection would be amplified and fiber contraction facilitated by SOICR. The circulation‐intact spinotrapezius muscle of adult male Wistar rats (n = 34) was exteriorized and loaded with Fura‐2 AM to monitor [Ca2+]i dynamics. Groups of rats underwent the following treatments: (1) 0.02, 0.2, and 2.0 mmol/L Ca2+ injections, (2) 2.0 mmol/L Ca2+ with inhibition of ryanodine receptors (RyR) by dantrolene sodium (DAN), and (3) 2.0 mmol/L Ca2+ with inhibition of SR Ca2+ ATPase (SERCA) by cyclopiazonic acid (CPA). A quantity of 0.02 mmol/L Ca2+ injection yielded no detectable response, whereas peak evoked [Ca2+]i increased 9.9 ± 1.8% above baseline for 0.2 mmol/L and 23.8 ± 4.3% (P < 0.05) for 2.0 mmol/L Ca2+ injections. The peak [Ca2+]i in response to 2.0 mmol/L Ca2+ injection was largely abolished by DAN and CPA (−85.8%, −71.0%, respectively, both P < 0.05 vs. unblocked) supporting dependence of the [Ca2+]i dynamics on Ca2+ released by SOICR rather than injected Ca2+ itself. Thus, this investigation demonstrates the presence of a robust SR‐evoked SOICR operant in skeletal muscle in vivo.

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“…Data obtained at the same time show that Zn 2+ has a biphasic modulatory effect on Ca 2+ regulatory sites on RYR (the channel does not pass into the active state unless a nmol concentration of Ca 2+ is present in its niche; it becomes inactive if Ca 2+ is present in concentrations greater than 1 μM). It should also be noted that the affinity of Ca 2+ on the binding sites changes significantly in the presence of Zn( 2+ ), whereas changes in Ca 2+ had no clear effect on the affinity of Zn 2+ on binding [ 64 ].…”

Section: Can Skeletal Muscle Be a Model For Testing The Hypothesis?mentioning

confidence: 99%

H2O2/Ca2+/Zn2+ Complex Can Be Considered a “Collaborative Sensor” of the Mitochondrial Capacity?

et al. 2022

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In order to maintain a state of well-being, the cell needs a functional control center that allows it to respond to changes in the internal and surrounding environments and, at the same time, carry out the necessary metabolic functions. In this review, we identify the mitochondrion as such an “agora”, in which three main messengers are able to collaborate and activate adaptive response mechanisms. Such response generators, which we have identified as H2O2, Ca2+, and Zn2+, are capable of “reading” the environment and talking to each other in cooperation with the mitochondrion. In this manner, these messengers exchange information and generate a holistic response of the whole cell, dependent on its functional state. In this review, to corroborate this claim, we analyzed the role these actors, which in the review we call “sensors”, play in the regulation of skeletal muscle contractile capacities chosen as a model of crosstalk between Ca2+, Zn2+, and H2O2.

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Biphasic modulation of ryanodine binding to sarcoplasmic reticulum vesicles of skeletal muscle by Zn2+ ions

Abstract: With the use of a [$H]ryanodine binding assay, the modulation of skeletal muscle ryanodine receptor (RyR1) by Zn# + was investigated. In the presence of 100 µM free Ca# + concentration (

Cited by 8 publications

References 17 publications

ß-Blocker Timolol Prevents Arrhythmogenic Ca2+ Release and Normalizes Ca2+ and Zn2+ Dyshomeostasis in Hyperglycemic Rat Heart

ß-Blocker Timolol Prevents Arrhythmogenic Ca2+ Release and Normalizes Ca2+ and Zn2+ Dyshomeostasis in Hyperglycemic Rat Heart

In vivo Ca²⁺ dynamics induced by Ca²⁺ injection in individual rat skeletal muscle fibers

H2O2/Ca2+/Zn2+ Complex Can Be Considered a “Collaborative Sensor” of the Mitochondrial Capacity?

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Biphasic modulation of ryanodine binding to sarcoplasmic reticulum vesicles of skeletal muscle by Zn2+ ions

Abstract: With the use of a [$H]ryanodine binding assay, the modulation of skeletal muscle ryanodine receptor (RyR1) by Zn# + was investigated. In the presence of 100 µM free Ca# + concentration (

Cited by 8 publications

References 17 publications

ß-Blocker Timolol Prevents Arrhythmogenic Ca2+ Release and Normalizes Ca2+ and Zn2+ Dyshomeostasis in Hyperglycemic Rat Heart

ß-Blocker Timolol Prevents Arrhythmogenic Ca2+ Release and Normalizes Ca2+ and Zn2+ Dyshomeostasis in Hyperglycemic Rat Heart

In vivo Ca2+ dynamics induced by Ca2+ injection in individual rat skeletal muscle fibers

H2O2/Ca2+/Zn2+ Complex Can Be Considered a “Collaborative Sensor” of the Mitochondrial Capacity?

Contact Info

Product

Resources

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In vivo Ca²⁺ dynamics induced by Ca²⁺ injection in individual rat skeletal muscle fibers