Basic principles of neuromuscular transmission

Martyn, J. A. Jeevendra; Fagerlund, Malin Jonsson; Eriksson, Lars

doi:10.1111/j.1365-2044.2008.05865.x

Cited by 83 publications

(55 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The issue of altered AChR expression numbers as well as shifts in expression profiles towards embryonic isoforms (464) in myopathy in critical illness is still puzzling with studies showing upregulation (214,460,639), downregulation (508), or no change at all (213,337), depending on the experimental model of critical illness (464). This is possibly due to the relative contribution of the isolated effects of systemic inflammation and sepsis, immobilization and denervation to the resulting overall AChR expression in each model.…”

Section: B Neuromuscular Transmission In Sepsis and Systemic Inflammmentioning

confidence: 99%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

292

329

View full text Add to dashboard Cite

Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca 2ϩ dysregulation is present through altered Ca 2ϩ homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.

show abstract

Section: B Neuromuscular Transmission In Sepsis and Systemic Inflammmentioning

confidence: 99%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

292

329

View full text Add to dashboard Cite

show abstract

“…γ-AChR is initially expressed in fetal muscle, and then replaced by ε-AChR when muscles are innervated. However, in some pathologic conditions (e.g., denervation), γ-AChR is re-expressed throughout the muscle membrane (Martyn et al, 2009;Fagerlund and Eriksson, 2009). The expression of γ-AChR has clinical significance, because the two subtypes have different electrophysiological and drug-binding properties (Martyn et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

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.

View full text Add to dashboard Cite

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.

show abstract

“…ACh immediately detaches from the receptor and is destroyed by the enzyme, acetylcholinesterase, which is also present in the cleft. 5 Depolarizing muscle relaxants can also act on these receptors to mimic the effect of Acetylcholine and cause depolarization of the end plate (Agonists of receptor). Nondepolarising muscle relaxants (NDMR) also act on the receptors, but they prevent ACh from binding to the receptor and thus prevent depolarization by agonists (Antagonists of receptor).…”

Section: Discussionmentioning

confidence: 99%