PMID- 11606634 OWN - NLM STAT- MEDLINE DCOM- 20011204 LR - 20240420 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 21 IP - 21 DP - 2001 Nov 1 TI - Sodium channel mRNAs at the neuromuscular junction: distinct patterns of accumulation and effects of muscle activity. PG - 8456-63 AB - 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" Na(V)1.4 and "fetal" Na(V)1.5 isoforms of VGSC in mammalian skeletal muscle, and used them in in situ hybridization studies of rat soleus muscles. Na(V)1.4 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. Na(V)1.5 mRNA is undetectable in innervated muscles but is dramatically upregulated by denervation. In muscles denervated for 1 week, both Na(V)1.4 and Na(V)1.5 mRNAs are present throughout the muscle, and both are concentrated at the NMJ. No Na(V)1.5 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 Na(V)1.4 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 Na(V)1.5 mRNA is downregulated by muscle activity, both at the NMJ and away from it. FAU - Awad, S S AU - Awad SS AD - Department of Neuroscience, University of Newcastle upon Tyne, NE2 4HH, Newcastle upon Tyne, United Kingdom. s.s.awad@ncl.ac.uk FAU - Lightowlers, R N AU - Lightowlers RN FAU - Young, C AU - Young C FAU - Chrzanowska-Lightowlers, Z M AU - Chrzanowska-Lightowlers ZM FAU - Lomo, T AU - Lomo T FAU - Slater, C R AU - Slater CR LA - eng GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Oligoribonucleotides, Antisense) RN - 0 (Protein Isoforms) RN - 0 (RNA, Messenger) RN - 0 (Sodium Channels) SB - IM MH - Animals MH - Autoradiography MH - Electric Stimulation/methods MH - Female MH - In Situ Hybridization MH - Muscle Contraction/physiology MH - Muscle Denervation MH - Muscle, Skeletal/innervation/*physiology MH - Neuromuscular Junction/*metabolism MH - Oligoribonucleotides, Antisense/genetics/metabolism MH - Polymerase Chain Reaction MH - Protein Isoforms/genetics/metabolism MH - RNA, Messenger/*metabolism MH - Rats MH - Rats, Wistar MH - Sodium Channels/genetics/*metabolism MH - Up-Regulation PMC - PMC6762790 EDAT- 2001/10/19 10:00 MHDA- 2002/01/05 10:01 PMCR- 2002/05/01 CRDT- 2001/10/19 10:00 PHST- 2001/10/19 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/10/19 10:00 [entrez] PHST- 2002/05/01 00:00 [pmc-release] AID - 21/21/8456 [pii] AID - 5762 [pii] AID - 10.1523/JNEUROSCI.21-21-08456.2001 [doi] PST - ppublish SO - J Neurosci. 2001 Nov 1;21(21):8456-63. doi: 10.1523/JNEUROSCI.21-21-08456.2001.