Different magnitude of resistance to nondepolarizing muscle relaxants in the denervated mouse skeletal muscle

Wang, Hong; Yang, Bin; Xu, Yu; Yan, Tao; Li, Shitong

doi:10.1038/aps.2010.26

Cited by 10 publications

(12 citation statements)

References 19 publications

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“…We also observed an increased percentage of immature γ-subunit. According to our previous study on the actions of the NDMRs tested at γ-and ε-nAChR expression in HEK293 cells, ATR was less potent at γ-nAChR than ε-nAChR, VEC was equipotent at both receptor subtypes, while ROC was more potent at γ-nAChR than ε-nAChR (Wang et al, 2010). Thus, the rank order of the magnitude of resistance to the three NDMRs in skeletal muscle with upregulation of immature nAChRs was ATR > VEC > ROC.…”

Section: Discussionmentioning

confidence: 87%

“…Our previous research suggested that the magnitude of denervation-induced resistance to NDMRs depends on the kind of neuromuscular blocker and is related to the different potencies of individual NDMRs on nAChR subunits (Wang et al, 2010). The hypothesis of this study was that chronic Dex treatment would cause different magnitudes of resistance to different NDMRs related to altered expression of nAChRs.…”

Section: Introductionmentioning

confidence: 83%

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Different magnitude of resistance to non-depolarizing muscle relaxants in dexamethasone-treated rat diaphragm associated with altered acetylcholine receptor expression

Chen¹,

Yang²,

Huang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to investigate the influence of chronic dexamethasone (Dex) administration on rat diaphragm sensitivity to non-depolarizing muscle relaxants (NDMRs) and muscular nicotinic acetylcholine receptor (nAChR) expression, which may help direct future administration of NDMRs. Adult male SpragueDawley rats were randomized to receive a daily intraperitoneal injection of Dex (600 μg/kg body mass) or an equivalent volume of saline (N = 20 in each group) for 14 days. We evaluated isometric twitch tensions of nerve-hemidiaphragm preparations elicited by indirect supramaximal stimulation at 0.1 Hz. Real-time quantitative PCR was performed to determine the mRNA expression of two nAChR subunits (ε-subunit and γ-subunit) in the diaphragm. Dex administration markedly (P < 0.01) increased the 50% twitch depression (IC 50 ) of the three NDMRs. The IC 50 ratio, which standardized the magnitudes of the resistance, was the Differential Dex-induced resistance to muscle relaxants largest for atracurium, with the second largest for vecuronium and the smallest for rocuronium (P < 0.01). The ε-and γ-subunit mRNAs were both upregulated with an increased γ/ε ratio in rats exposed to Dex. The results indicated that chronic Dex administration induces hyposensitivity to NDMRs, the degree of which depends on the kind of neuromuscular blocker, and is associated with increased nAChR expression.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 83%

Different magnitude of resistance to non-depolarizing muscle relaxants in dexamethasone-treated rat diaphragm associated with altered acetylcholine receptor expression

Chen¹,

Yang²,

Huang³

et al. 2014

Genet. Mol. Res.

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“…This concentration can ensure sufficient acetylcholine current responses and minimize the desensitization of the nicotinic acetylcholine receptor that resulted from the repetitive application of acetyl choline [13,14] . In this study, the HEK293 cells were clamped at -80 mV because the antagonistic effects of nondepolarizing muscle relaxants are independent of the holding voltages that range from -100 to -40 mV [13,15,19,20] .…”

Section: Wwwchinapharcom Wang H Et Almentioning

confidence: 99%

Magnesium sulfate enhances non-depolarizing muscle relaxant vecuronium action at adult muscle-type nicotinic acetylcholine receptor in vitro

et al. 2011

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Aim:To investigate the effect of magnesium sulfate and its interaction with the non-depolarizing muscle relaxant vecuronium at adult muscle-type acetylcholine receptors in vitro. Methods: Adult muscle-type acetylcholine receptors were expressed in HEK293 cells. Drug-containing solution was applied via a gravity-driven perfusion system. The inward currents were activated by brief application of acetylcholine (ACh), and recorded using whole-cell voltage-clamp technique. Results: Magnesium sulfate (1-100 mmol/L) inhibited the inward currents induced ACh (10 μmol/L) in a concentration-dependent manner (IC 50 =29.2 mmol/L). The inhibition of magnesium sulfate was non-competitive. In contrast, vecuronium produced a potent inhibition on the adult muscle-type acetylcholine receptor (IC 50 =8.7 nmol/L) by competitive antagonism. Magnesium sulfate at the concentrations of 1, 3, and 6 mmol/L markedly enhanced the inhibition of vecuronium (10 nmol/L) on adult muscle-type acetylcholine receptors. Conclusion: Clinical enhancement of vecuronium-induced muscle relaxation by magnesium sulfate can be attributed partly to synergism between magnesium sulfate and non-depolarizing muscle relaxants at adult muscle-type acetylcholine receptors.

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“…However, our study showed that skeletal muscle did not become resistant to vecuronium at Day 1 after denervation. Wang et al [25] observed that post-denervation resistance to atracurium was greater than to vecuronium, which is due to the different potencies of atracurium and vecuronium on nAChR subunits. In addition to having a similar structure to that of atracurium, dTC also has less potency on γ-AChR than on ε-AChR and has partial agonist effects on γ-AChR [13,18,26] .…”

Section: Wwwchinapharcom Wang H Et Almentioning

confidence: 99%

Potency of nondepolarizing muscle relaxants on muscle-type acetylcholine receptors in denervated mouse skeletal muscle

et al. 2010

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Aim: To investigate the changing resistance to nondepolarizing muscle relaxants (NDMRs) during the first month after denervation. Methods: The denervated and innervated skeletal muscle cells were examined on days 1, 4, 7, 14, 21, and 28 after denervation. Individual denervated and innervated cells were prepared from the flexor digitorum brevis of the surgically denervated and contralateral hind feet, respectively. Nicotinic acetylcholine receptors (nAChRs) in the cells were activated with 30 µmol/L acetylcholine, either alone or in combination with various concentrations of vecuronium. Currents were recorded using a whole-cell patch-clamp technique. Results: The concentrations of vecuronium resulting in half-maximal inhibitory responses (IC 50 ) increased 1.2-(P>0.05), 1.7-, 3.7-, 2.5-, 1.9-, and 1.8-fold (P<0.05) at Days 1, 4, 7, 14, 21, and 28 after denervation, respectively, compared to the innervated control. Resistance to vecuronium appeared at Day 4, peaked at Day 7, and declined at Day 14 after denervation. Nevertheless, IC 50 values at Day 28 remained significantly higher than those for the innervated control, suggesting that the resistance to vecuronium had not disappeared at Day 28. Conclusion: The NDMR doses required to achieve satisfactory clinical effects differ at different times after muscle denervation.

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Different magnitude of resistance to nondepolarizing muscle relaxants in the denervated mouse skeletal muscle

Cited by 10 publications

References 19 publications

Different magnitude of resistance to non-depolarizing muscle relaxants in dexamethasone-treated rat diaphragm associated with altered acetylcholine receptor expression

Different magnitude of resistance to non-depolarizing muscle relaxants in dexamethasone-treated rat diaphragm associated with altered acetylcholine receptor expression

Magnesium sulfate enhances non-depolarizing muscle relaxant vecuronium action at adult muscle-type nicotinic acetylcholine receptor in vitro

Potency of nondepolarizing muscle relaxants on muscle-type acetylcholine receptors in denervated mouse skeletal muscle

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