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Sodium channel mRNAs at the neuromuscular junction: Distinct patterns of accumulation and effects of muscle activity

Lookup NU author(s): Suad Awad, Professor Robert Lightowlers, Professor Zofia Chrzanowska-Lightowlers, Emeritus Professor Clarke Slater

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Abstract

Voltage-gated sodium channels (VGSCs) are highly concentrated at the neuromuscular junction (NMJ) in mammalian skeletal muscle. Here we test the hypothesis that local upregulation of mRNA contributes to this accumulation. We designed radiolabeled antisense RNA probes, specific for the "adult" Nav1.4 and "fetal" Nav1.5 isoforms of VGSC in mammalian skeletal muscle, and used them in in situ hybridization studies of rat soleus muscles. Nav1.4 mRNA is present throughout normal adult muscles but is highly concentrated at the NMJ, in which the amount per myonucleus is more than eightfold greater than away from the NMJ. Nav1.5 mRNA is undetectable in innervated muscles but is dramatically upregulated by denervation. In muscles denervated for 1 week, both Nav1.4 and Nav1.5 mRNAs are present throughout the muscle, and both are concentrated at the NMJ. No Nav1.5 mRNA was detectable in denervated muscles stimulated electrically for 1 week in vivo. Neither denervation nor stimulation had any significant effect on the level or distribution of Nav1.4 mRNA. We conclude that factors, probably derived from the nerve, lead to the increased concentration of VGSC mRNAs at the NMJ. In addition, the expression of Nav1.5 mRNA is downregulated by muscle activity, both at the NMJ and away from it.


Publication metadata

Author(s): Awad SS, Lightowlers RN, Young C, Chrzanowska-Lightowlers ZMA, Lomo T, Slater CR

Publication type: Article

Publication status: Published

Journal: Journal of Neuroscience

Year: 2001

Volume: 21

Issue: 21

Pages: 8456-8463

ISSN (print): 0270-6474

ISSN (electronic): 1529-2401

Publisher: Society for Neuroscience

PubMed id: 11606634


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