Channel activators reduce the expression of sodium channel α-subunit mRNA in developing neurons

Lara, Agnès; Julien, F.; Alcaraz, Gisèle; Tricaud, Nicolas; Courand, François; Jover, Emmanuel

doi:10.1016/0169-328x(95)00286-2

Cited by 18 publications

(15 citation statements)

References 25 publications

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“…Our present results also differ slightly from that reported by Lara et al (1996) in primary cultured neurons. However, their studies used a non-quantitative RT/PCR technique where the abundance of Navl.3 channel mRNA was reported to be maximal, followed by Na,1.2 and Na1.1 (Na,1.7 and Nay1.8 genes were not studied).…”

Section: Discussioncontrasting

confidence: 99%

“…Also, in primary neuronal that the ischemic insult also affects neuronal activity cultures from rats scorpion neurotoxin (a sodium (and likely membrane conductance) in the contrachannel agonist) decreased the expression of Na,1.1, lateral hemisphere. In this context, using in situ Na,1.2, and Navl.3 (Lara et al, 1996) and in rats with hybridization for the Nav1.1 gene we have discovkainite-induced seizures, the down-regulation of ered that the expression of this gene is in fact Nav1.2 and Na,1.3 (adult subtype) NaCh gene decreased on the contralateral hemisphere at 24h expression in the hippocampus has also been post-MCAo . Additional studies documented (Gastaldi et al, 1997), indicating that are currently in progress evaluating more time points persistent activation may relate to a molecular and and the other NaCh genes.…”

Section: 00mentioning

confidence: 99%

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Neuronal Sodium Channels in Neurodegeneration and Neuroprotection

Tortella¹

2002

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathe0 ng and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Infonnation Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and Approved for Public Release; Distribution Unlimited ABSTRACT (Maximum 200 Words)The purpose of this research project is to study the role of neuronal sodium channels in mechanisms of neuronal injury, neurodegeneration, and neuroprotection. The primary objective of this research project is to characterize the expression, and study the functional significance, of neuronal sodium channels during the process of injury and recovery. Also, the effects of sodium channel blockade (using antisense and channel blockers) on gene expression and neurodegeneration will be studies.The progress during our 3rd year of this project wss excellent. Several important and critical discoveries providing a greater understanding of the injury/neurodegeneration process and the role of brain NAChs in this process were elucidated. Our key observations were 1) using ASO for the Nal.1 NaCh it was demonstrated that functional blockade of this channel results in brain neuroprotection following injury; 2) our in situ hybridization experiments defined the regional anatomical distribution of Navl.1 sodium channel gene expression in normal and at various time-post MCAo and confirmed our QRT-PCR data showing the Nal .1 expression to be down-regulated in subcortical and cortical regions of injured and, to some degree of contralateral hemispheres. In addition, these in situ hybridization studies revealed that the expression of other NaCh gene appears not to be of significance to the brain injury process; 3) our preliminary results show that treatment of neurons with RS-1000642 at least partially reverses the down-regulation of Navl .1 caused by MCAo injury. Importantly, evidendc eindicates that this is an effect selective for the Nal.1 NaCh and not other NAChs; 4) Based upon our QRT-PCR resutls, it does not appear that sodium-calcium exhanger genes, namely NCXl, NCX2 and NCX3, re inolved in the NaCh mechanisms of ischemia brain injury, at least not at early time-points post-MCAo injury; 4) Finally, our comprehensive EEG studies have identified several non-convulsant (NCS) brain seizure events identical to the clinical brain injury and that of all the AEDs tested to date, only the sodium channel blocker RS-100642 significantly stops or attenuates the NCS neuropathology. received considerable attention, leading many, including our own laboratory, to propose the "calcium mechanism" of neuronal injury and neurodegeneration. However, of possibly equal consequence to t...

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Section: Discussioncontrasting

confidence: 99%

Section: 00mentioning

confidence: 99%

Neuronal Sodium Channels in Neurodegeneration and Neuroprotection

Tortella¹

2002

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“…2, [11]) contains all of these hallmarks. Consistent with its splicing, transcripts lacking this insert account for the majority ofthefll mRNA ( [11,12] and this study). Additionally, the human ,81 gene structure has already been published and an intron of 90 bp (intron 5) is reported to be present at precisely the same location as the insert in/31.2, but the complete sequence of this intron was not reported [19].…”

Section: Resultsmentioning

confidence: 72%

“…Also, the length of intron 5 (86-90 bp) is more typical of internal introns than of introns occurring in the 3' untranslated sequences [24]. Intron 5 is the shortest intron in the human fll gene [19] and, interestingly, the only intron to be retained in the fl12 mRNA isoform ( [11,12] and this study). The presence offl~.z RNA is consistent with recent published reports which demonstrate the accumulation of unspliced, polyadenylated RNA as an intermediate during mRNA maturation [26]; the presence of a functional terminal intron is essential for the selection of a polyadenylation site and proper 3' end formation [271.…”

Section: Resultsmentioning

confidence: 99%

“…Amplification of similar DNA fragments is also reported from embryonic rat tissues [12]. In the present study we used RT-PCR and genomic PCR to investigate the presence of the two fll isoforms and to determine the source of ilL> In an attempt to determine if the fll subunit is encoded by members of a gene family, we analysed cDNA fragments that were amplified by RT-PCR from various adult rat tissue RNAs.…”

Section: Introductionmentioning

confidence: 99%

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Genes encoding the β1 subunit of voltage‐dependent Na⁺ channel in rat, mouse and human contain conserved introns

1995

FEBS Letters

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We provide evidence in this study that the 86-bp insert in the/$L2 mRNA isoform of the voltage gated sodium channel is an intron. Transcripts still retaining this intron were detected in all tissues where the IBI gene expression was investigated. We also show that the exon/intron boundaries of the last two introns are conserved among rat, mouse and human ~1 gene. Unlike the highly conserved cDNAs, introns in only the rat and mouse genes are highly related. The last intron is very short (86-90 bp) and is located in the 3' untranslated sequence, both uncommon properties of mammalian pre-mRNA introns.

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Role of Calcium and Calpain in the Downregulation of Voltage‐Gated Sodium Channel Expression by the Pyrethroid Pesticide Deltamethrin

Magby

Richardson

2014

J Biochem & Molecular Tox

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Voltage-gated sodium channels (Nav) are essential for initiation and propagation of action potentials. Previous in vitro studies reported that exposure to the Nav toxins veratridine and α scorpion toxin cause persistent downregulation of Nav mRNA in vitro. However the mechanism of this downregulation is not well characterized. Here, we report that the type-II pyrethroid deltamethrin, which has a similar mechanism as these toxins, elicited an approximate 25% reduction in Nav 1.2 and Nav 1.3 mRNA in SK-N-AS cells. Deltamethrin-induced decreases of Nav mRNA were blocked with the Nav antagonist tetrodotoxin, demonstrating a primary role for interaction with Nav. Pre-treatment with the intracellular calcium chelator BAPTA-AM and the calpain inhibitor PD-150606 also prevented these decreases, identifying a role for intracellular calcium and calpain activation. Because alterations in Nav expression and function can result in neurotoxicity, additional studies are warranted to determine whether or not such effects occur in vivo.

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Channel activators reduce the expression of sodium channel α-subunit mRNA in developing neurons

Cited by 18 publications

References 25 publications

Neuronal Sodium Channels in Neurodegeneration and Neuroprotection

Neuronal Sodium Channels in Neurodegeneration and Neuroprotection

Genes encoding the β1 subunit of voltage‐dependent Na⁺ channel in rat, mouse and human contain conserved introns

Role of Calcium and Calpain in the Downregulation of Voltage‐Gated Sodium Channel Expression by the Pyrethroid Pesticide Deltamethrin

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Channel activators reduce the expression of sodium channel α-subunit mRNA in developing neurons

Cited by 18 publications

References 25 publications

Neuronal Sodium Channels in Neurodegeneration and Neuroprotection

Neuronal Sodium Channels in Neurodegeneration and Neuroprotection

Genes encoding the β1 subunit of voltage‐dependent Na+ channel in rat, mouse and human contain conserved introns

Role of Calcium and Calpain in the Downregulation of Voltage‐Gated Sodium Channel Expression by the Pyrethroid Pesticide Deltamethrin

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Genes encoding the β1 subunit of voltage‐dependent Na⁺ channel in rat, mouse and human contain conserved introns