Exon 11 skipping of<i>SCN10A</i>coding for voltage-gated sodium channels in dorsal root ganglia

Schirmeyer, Jana; Szafranski, Karol; Leipold, Enrico; Mawrin, Christian; Platzer, Matthias; Heinemann, Stefan H.

doi:10.4161/chan.28146

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…In several mammals DRG neurons, alternative splicing of Na V α-subunit genes has been detected, resulting in the expression of multiple proteins. However, the functional significance of this process has not been completely elucidated ( Dietrich et al, 1998 ; Schirmeyer et al, 2014 ). Some variants seem to lead to subunits showing redundant or no obvious pharmacological and/or functional differences, compared with the wild-type subunit ( Schirmeyer et al, 2014 ).…”

Section: Voltage-gated Sodium Channels Expressed In Drg Neuronsmentioning

confidence: 99%

“…However, the functional significance of this process has not been completely elucidated ( Dietrich et al, 1998 ; Schirmeyer et al, 2014 ). Some variants seem to lead to subunits showing redundant or no obvious pharmacological and/or functional differences, compared with the wild-type subunit ( Schirmeyer et al, 2014 ). However, different pharmacological and functional properties between variant and wild-type subunits are evidenced in the literature, such as their sensitivity to drugs/toxins ( Dietrich et al, 1998 ; Tan et al, 2002 ; Thompson et al, 2011 ; Boullot et al, 2017 ), their functional specificity regarding tissue/cell localization ( Song et al, 2004 ), and their involvement in membrane excitability via the regulation of translational repression ( Lin and Baines, 2015 ).…”

Section: Voltage-gated Sodium Channels Expressed In Drg Neuronsmentioning

confidence: 99%

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The NaV1.7 Channel Subtype as an Antinociceptive Target for Spider Toxins in Adult Dorsal Root Ganglia Neurons

et al. 2018

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Although necessary for human survival, pain may sometimes become pathologic if long-lasting and associated with alterations in its signaling pathway. Opioid painkillers are officially used to treat moderate to severe, and even mild, pain. However, the consequent strong and not so rare complications that occur, including addiction and overdose, combined with pain management costs, remain an important societal and economic concern. In this context, animal venom toxins represent an original source of antinociceptive peptides that mainly target ion channels (such as ASICs as well as TRP, CaV, KV and NaV channels) involved in pain transmission. The present review aims to highlight the NaV1.7 channel subtype as an antinociceptive target for spider toxins in adult dorsal root ganglia neurons. It will detail (i) the characteristics of these primary sensory neurons, the first ones in contact with pain stimulus and conveying the nociceptive message, (ii) the electrophysiological properties of the different NaV channel subtypes expressed in these neurons, with a particular attention on the NaV1.7 subtype, an antinociceptive target of choice that has been validated by human genetic evidence, and (iii) the features of spider venom toxins, shaped of inhibitory cysteine knot motif, that present high affinity for the NaV1.7 subtype associated with evidenced analgesic efficacy in animal models.

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Section: Voltage-gated Sodium Channels Expressed In Drg Neuronsmentioning

confidence: 99%

Section: Voltage-gated Sodium Channels Expressed In Drg Neuronsmentioning

confidence: 99%

The NaV1.7 Channel Subtype as an Antinociceptive Target for Spider Toxins in Adult Dorsal Root Ganglia Neurons

et al. 2018

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“…One could hypothesize, therefore, that inflammation may decrease nociceptive neuronal excitability through Na v downregulation. However, Na v 1.7, as well as other Na v isoforms, can undergo alternative splicing, with each splice variant possessing distinct biochemical and pharmacological properties ( Schaller et al, 1992 ; Plummer et al, 1997 ; Dietrich et al, 1998 ; Schirmeyer et al, 2014 ). It was previously shown that a particular Na v 1.7 splice variant, Na v 1.7 11S, was upregulated and responsible for pain hypersensitivity in animal models of neuropathic pain ( Raymond et al, 2004 ).…”

Section: Protein Kinasesmentioning

confidence: 99%

Post-translational modifications of voltage-gated sodium channels in chronic pain syndromes

2015

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In the peripheral sensory nervous system the neuronal expression of voltage-gated sodium channels (Navs) is very important for the transmission of nociceptive information since they give rise to the upstroke of the action potential (AP). Navs are composed of nine different isoforms with distinct biophysical properties. Studying the mutations associated with the increase or absence of pain sensitivity in humans, as well as other expression studies, have highlighted Nav1.7, Nav1.8, and Nav1.9 as being the most important contributors to the control of nociceptive neuronal electrogenesis. Modulating their expression and/or function can impact the shape of the AP and consequently modify nociceptive transmission, a process that is observed in persistent pain conditions. Post-translational modification (PTM) of Navs is a well-known process that modifies their expression and function. In chronic pain syndromes, the release of inflammatory molecules into the direct environment of dorsal root ganglia (DRG) sensory neurons leads to an abnormal activation of enzymes that induce Navs PTM. The addition of small molecules, i.e., peptides, phosphoryl groups, ubiquitin moieties and/or carbohydrates, can modify the function of Navs in two different ways: via direct physical interference with Nav gating, or via the control of Nav trafficking. Both mechanisms have a profound impact on neuronal excitability. In this review we will discuss the role of Protein Kinase A, B, and C, Mitogen Activated Protein Kinases and Ca++/Calmodulin-dependent Kinase II in peripheral chronic pain syndromes. We will also discuss more recent findings that the ubiquitination of Nav1.7 by Nedd4-2 and the effect of methylglyoxal on Nav1.8 are also implicated in the development of experimental neuropathic pain. We will address the potential roles of other PTMs in chronic pain and highlight the need for further investigation of PTMs of Navs in order to develop new pharmacological tools to alleviate pain.

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Sodium Channel Trafficking

Mercier

Bois

Chatelier

2017

Voltage-Gated Sodium Channels: Structure, Function and Channelopathies

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Voltage-gated sodium channels (VGSC) are critical determinants of cellular electrical activity through the control of initiation and propagation of action potential. To ensure this role, these proteins are not consistently delivered to the plasma membrane but undergo drastic quality controls throughout various adaptive processes such as biosynthesis, anterograde and retrograde trafficking, and membrane targeting. In pathological conditions, this quality control could lead to the retention of functional VGSC and is therefore the target of different pharmacological approaches. The present chapter gives an overview of the current understanding of the facets of VGSC life cycle in the context of both cardiac and neuronal cell types.

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Exon 11 skipping ofSCN10Acoding for voltage-gated sodium channels in dorsal root ganglia

Abstract: (2014) Exon 11 skipping of SCN10A coding for voltage-gated sodium channels in dorsal root ganglia, Channels, 8:3,[210][211][212][213][214][215]

Cited by 4 publications

References 22 publications

The NaV1.7 Channel Subtype as an Antinociceptive Target for Spider Toxins in Adult Dorsal Root Ganglia Neurons

The NaV1.7 Channel Subtype as an Antinociceptive Target for Spider Toxins in Adult Dorsal Root Ganglia Neurons

Post-translational modifications of voltage-gated sodium channels in chronic pain syndromes

Sodium Channel Trafficking

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