Sodium Channel Regulation of Skeletal Muscle Membrane Excitability<sup>a</sup>

Ruff, Robert L.

doi:10.1111/j.1749-6632.1997.tb48618.x

Cited by 8 publications

(10 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5) but in agreement with previous studies examining the effect of β 2 ‐agonists on muscle (for review see Clausen, 2003), the activity of muscle Na + –K + pumps was increased as judged from the increase in the ouabain‐sensitive 86 Rb + uptake. The increased Na + –K + pump activity was associated with a decrease in the intracellular Na + and a hyperpolarization of 3.8 mV, which most probably improve muscle excitability via the ensuing increase in the electrochemical gradient for Na + and the relief of some of the inactivation of Na + channels (Ruff, 1997; Ruff et al 1988; Rich & Pinter, 2003). In contrast, acidification of the muscles by addition of lactic acid had no effect on the ouabain‐sensitive 86 Rb + uptake, the intracellular Na + content or the membrane potential.…”

Section: Discussionmentioning

confidence: 99%

Additive protective effects of the addition of lactic acid and adrenaline on excitability and force in isolated rat skeletal muscle depressed by elevated extracellular K⁺

Paoli

Overgaard

Pedersen

et al. 2007

The Journal of Physiology

View full text Add to dashboard Cite

During strenuous exercise, extracellular K + ([K+] o ) is increased, which potentially can reduce muscle excitability and force production. In addition, exercise leads to accumulation of lactate and H + and increased levels of circulating catecholamines. Individually, reduced pH and increased catecholamines have been shown to counteract the depressing effect of elevated K + . This study examines (i) whether the effects of addition of lactic acid and adrenaline on the excitability of isolated muscles are caused by separate mechanisms and are additive and (ii) whether the effect of adding lactic acid or increasing CO 2 is related to a reduction of intra-or extracellular pH. Rat soleus muscles were incubated at a [K + ] o of 15 mM, which reduced tetanic force by 85%. Subsequent addition of 20 mM lactic acid or 10 −5 M adrenaline led to a small recovery of force, but when added together induced an almost complete force recovery. Compound action potentials showed that the force recovery was associated with recovery of muscle excitability. The improved excitability after addition of adrenaline was associated with increased Na + -K + pump activity resulting in hyperpolarization and an increase in the chemical Na + gradient. In contrast, addition of lactic acid had no effect on the membrane potential or the Na + -K + pump activity, but most likely increased excitability via a reduction in intracellular pH. It is concluded that the protective effects of acidosis and adrenaline on muscle excitability and force took place via different mechanisms and were additive. The results suggest that circulating catecholamines and development of acidosis during exercise may improve the tolerance of muscles to elevated [K + ] o .

show abstract

Section: Discussionmentioning

confidence: 99%

Additive protective effects of the addition of lactic acid and adrenaline on excitability and force in isolated rat skeletal muscle depressed by elevated extracellular K⁺

Paoli

Overgaard

Pedersen

et al. 2007

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…Voltage-gated sodium channels in the adult skeletal muscle (Na v 1.4) determine the membrane excitability of the muscle fiber sarcolemma (599) and are important to initiate the upstroke phase of the action potential upon crossing a certain membrane potential threshold for channel opening during membrane depolarization. This potential threshold is mainly set by the steady-state inac-tivation of the channels (253,270).…”

Section: A Sodium Channels Determine Membrane Excitability In Skeletmentioning

confidence: 99%

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

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

293

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

“…Different types of muscle fibre display different Na + channel properties tuned to their contractile requirements. Na + currents in fast-twitch fibres have more negative V 1/2 values for voltage dependence of inactivation and larger current densities in the end-plate and endplate border than slow-twitch fibres [18,25]. These differences could reflect different combinations of SkM1 with β1 or β3.…”

Section: Discussionmentioning

confidence: 88%

“…Muscle fibres can be classified as fast-twitch glycolytic (type IIb), fast-twitch-oxidative-glycolytic (type IIa) and slow-twitch-oxidative (type I) by their differences in physiology and histochemistry; for example, contractile properties, fatigue resistance and myosin heavy chain isoform [25]. Different types of muscle fibre display different Na + channel properties tuned to their contractile requirements.…”

Section: Discussionmentioning

confidence: 99%

Tissue distribution and functional expression of the human voltage-gated sodium channel β3 subunit

Stevens

Cox

Shah

et al. 2001

Pfl�gers Archiv European Journal of Physiology

View full text Add to dashboard Cite

This study investigated the distribution of beta3 in human tissues and the functional effects of the human beta3 subunit on the gating properties of brain and skeletal muscle alpha subunits. Using RT-PCR of human cDNA panels, beta3 message was detected in brain, heart, kidney, lung, pancreas and skeletal muscle. Both alphaIIA and SkM1 expressed in Xenopus oocytes inactivated with a time course described by two exponential components representing fast and slow gating modes, while co-expression of human beta3 with alphaIIA or SkM1 significantly increased the proportion of channels operating by the fast gating mode. In the presence of beta3 a greater proportion of alphaIIA or SkM1 current was described by the fast time constant for both inactivation and recovery from inactivation. beta3 caused a hyperpolarizing shift in the voltage dependence of inactivation of alphaIIIA and reduced the slope factor. The voltage dependence of inactivation of SkM1 was described by a double Boltzmann equation. However, SkM1 co-expressed with beta3 was described by a single Boltzmann equation similar to one of the Boltzmann components for SkM1 expressed alone, with a small positive shift in V1/2 value and reduced slope factor. This is the first study demonstrating that beta3 is expressed in adult mammalian skeletal muscle and can functionally couple to the skeletal muscle alpha subunit, SkM1.

show abstract

Sodium Channel Regulation of Skeletal Muscle Membrane Excitability^a

Cited by 8 publications

References 56 publications

Additive protective effects of the addition of lactic acid and adrenaline on excitability and force in isolated rat skeletal muscle depressed by elevated extracellular K⁺

Additive protective effects of the addition of lactic acid and adrenaline on excitability and force in isolated rat skeletal muscle depressed by elevated extracellular K⁺

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

Tissue distribution and functional expression of the human voltage-gated sodium channel β3 subunit

Contact Info

Product

Resources

About

Sodium Channel Regulation of Skeletal Muscle Membrane Excitabilitya

Cited by 8 publications

References 56 publications

Additive protective effects of the addition of lactic acid and adrenaline on excitability and force in isolated rat skeletal muscle depressed by elevated extracellular K+

Additive protective effects of the addition of lactic acid and adrenaline on excitability and force in isolated rat skeletal muscle depressed by elevated extracellular K+

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

Tissue distribution and functional expression of the human voltage-gated sodium channel β3 subunit

Contact Info

Product

Resources

About

Sodium Channel Regulation of Skeletal Muscle Membrane Excitability^a

Additive protective effects of the addition of lactic acid and adrenaline on excitability and force in isolated rat skeletal muscle depressed by elevated extracellular K⁺

Additive protective effects of the addition of lactic acid and adrenaline on excitability and force in isolated rat skeletal muscle depressed by elevated extracellular K⁺