Effects of chronic sepsis on the voltage-gated sodium channel in isolated rat muscle fibers*

Rossignol, Benoît; Guéret, Gildas; Pennec, Jean-Pierre; Morel, Julie; Giroux-Metgès, Marie-Agnès; Talarmin, Hélène; Arvieux, C. C.

doi:10.1097/01.ccm.0000254335.88023.0e

Cited by 57 publications

(43 citation statements)

References 32 publications

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“…In steroid-treated, denervated rat muscle, it was found that a combination of depolarization of the resting potential and a hyperpolarized shift in the voltage dependence of sodium channel inactivation resulted in unexcitability of the majority of muscle fibers (196, 580 -582). The voltage dependence of sodium channel inactivation was also found to be shifted in the hyperpolarized direction by pure sepsis in the rat (594). These data suggest that increased inactivation of sodium channels is a major contributor to reduced excitability.…”

Section: B "Sodium Channelopathy" In Muscle Inmentioning

confidence: 71%

“…In innervated mature skeletal muscle, only the Na v 1.4 sodium channel isoform is expressed. After denervation, steroid treatment, or sepsis, there is upregulation of the Na v 1.5 isoform (578,594,789). Normally, the Na v 1.5 isoform is expressed in embryonic skeletal muscle but is downregulated during development (790).…”

Section: B "Sodium Channelopathy" In Muscle Inmentioning

confidence: 99%

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

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

291

329

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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.

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Section: B "Sodium Channelopathy" In Muscle Inmentioning

confidence: 71%

Section: B "Sodium Channelopathy" In Muscle Inmentioning

confidence: 99%

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

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

291

329

View full text Add to dashboard Cite

show abstract

“…Not all fibres are affected to the same extent and the percentage affected determines the severity of weakness [17]. Increased NaV1.5 has also been shown in a model of chronic sepsis in rats [103] and lipopolysaccharide interaction with and disruption of the channel has been demonstrated in vitro [104]. However, these effects have yet to be shown in ICUAW muscle.…”

Section: Electrical Inexcitabilitymentioning

confidence: 99%

Molecular mechanisms of intensive care unit-acquired weakness

Bloch¹,

Polkey²,

Griffiths³

et al. 2011

Eur Respir J

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Intensive care unit-acquired weakness (ICUAW) is an increasingly recognised and important clinical consequence of critical illness. It is associated with significant morbidity and mortality. The aetiology of this disease is not well understood. The purpose of this article is to review our understanding of the molecular pathogenesis of ICUAW in the context of current knowledge of clinical risk factors and aetiology.Key features of the disease are loss of muscle mass resulting from a shift in the dynamic balance of muscle protein synthesis and breakdown and a reduction in force-generating capacity. These alternations are secondary to neuropathy, disruption of the myofilament structure and function, a disrupted sarcoplasmic reticulum, electrical inexcitability and bioenergenetic failure.As knowledge and understanding of ICUAW grows, potential therapeutic targets will be identified, hopefully leading to multiple strategies for prevention and treatment of this important condition.

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“…Upregulation of NaV1.5 sodium channels has been demonstrated in the muscle of rats with chronic sepsis, suggesting that several risk factors lead to muscle electrical nonexcitability [79]. A negative shift in sodium channel gating in peripheral nerves of muscle is distinguished from CIM as a characteristic disorder in CIP [80].…”

Section: Physical Disabilities -Therapeutic Implicationsmentioning

confidence: 99%

Skeletal Muscle Dysfunction in Critical Illness

Iida¹,

Sakuma²

2017

Physical Disabilities - Therapeutic Implications

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Despite improvements in critical illness survival rates with recent developments in medical care, many patients still have long-term physical disabilities following stays in the intensive care unit (ICU). Critical illness-induced muscle weakness, so-called ICU-acquired weakness (ICU-AW), is a common occurrence in approximately 50% of critically ill patients in the ICU requiring mechanical ventilation for >7 days. ICU-AW contributes to increases in duration of mechanical ventilation and lengths of ICU and hospital stays and may persist among survivors for several years after discharge. Risk factors for ICU-AW include systemic inflammatory responses, severe sepsis, muscle inactivity, hyperglycemia, and use of neuromuscular blockers. Thus, the development of muscle wasting is suggested to be associated with pathophysiological alterations leading to an imbalance between muscle proteolysis and proteosynthesis through several cellular signaling networks. This chapter presents a review of the literature regarding critical illness-induced muscle wasting and describes potential treatment of excessive muscle catabolism.

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Effects of chronic sepsis on the voltage-gated sodium channel in isolated rat muscle fibers*

Cited by 57 publications

References 32 publications

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

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

Molecular mechanisms of intensive care unit-acquired weakness

Skeletal Muscle Dysfunction in Critical Illness

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