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The Journal of Neuroscience, November 1, 2001, 21(21):8456-8463

Sodium Channel mRNAs at the Neuromuscular Junction: Distinct Patterns of Accumulation and Effects of Muscle Activity

Suad S. Awad¹, Robert N. Lightowlers¹, Carol Young¹, Zofia M. A. Chrzanowska-Lightowlers¹, Terje Lømo², and Clarke R. Slater¹

¹ Department of Neuroscience, University of Newcastle upon Tyne, NE2 4HH, Newcastle upon Tyne, United Kingdom, and ² Department of Physiology, University of Oslo, 0317 Oslo, Norway

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_V1.4 and "fetal" Na_V1.5 isoforms of VGSC in mammalian skeletal muscle, and used them in in situ hybridization studies of rat soleus muscles. Na_V1.4 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_V1.5 mRNA is undetectable in innervated muscles but is dramatically upregulated by denervation. In muscles denervated for 1 week, both Na_V1.4 and Na_V1.5 mRNAs are present throughout the muscle, and both are concentrated at the NMJ. No Na_V1.5 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_V1.4 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_V1.5 mRNA is downregulated by muscle activity, both at the NMJ and away from it.

Key words: neuromuscular junction; sodium channels; denervation; electrical activity; rat; in situ hybridization

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21218456-08$05.00/0

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