Expression and distribution of sodium channels in short- and long-term denervated rodent skeletal muscles

• Published in: The Journal of physiology 1995-02, Vol.483 (Pt 1), p.109-118
• Main Authors: Lupa, M T, Krzemien, D M, Schaller, K L, Caldwell, J H
• Format: Article
• Language: English
• Subjects: Animals; Membrane Potentials - physiology; Mice; Muscle Denervation; Muscle, Skeletal - cytology; Muscle, Skeletal - innervation; Muscle, Skeletal - metabolism; Neuromuscular Junction - metabolism; Patch-Clamp Techniques; Rats; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Sodium - metabolism; Sodium Channels - genetics; Sodium Channels - metabolism; Tetrodotoxin - pharmacology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.1995.sp020571

1. Loose-patch voltage-clamp recordings were made from rat and mouse skeletal muscle fibres denervated for up to 6 weeks. Innervated muscles possessed a Na+ current density of 107 +/- 3.3 mA cm-2 in endplate membrane, and 6.3 +/- 0.6 mA cm-2 in extrajunctional membrane. This high concentration of Na+ channels at the endplate was gradually reduced following denervation. After 6 weeks of denervation, the endplate Na+ channel concentration was reduced by 40-50%, and the density of Na+ channels in extrajunctional membrane was increased by about 30%. 2. The tetrodotoxin (TTX)-resistant form of the Na+ channel appeared after 3 days of denervation and comprised approximately 43% of the endplate Na+ channels 5-6 days after denervation. Subsequently, TTX-resistant Na+ channels were reduced in density to approximately 25% of the postjunctional Na+ channels and remained at this level up to 6 weeks after denervation. 3. RNase protection analysis showed that mRNA encoding the TTX-resistant Na+ channel was virtually absent in innervated muscle, rose > 50-fold after 3 days of denervation, then decreased by 95% 6 weeks after denervation. The density of TTX-resistant Na+ channels correlated qualitatively with changes in mRNA levels. 4. These results suggest that the density of Na+ channels at neuromuscular junctions is maintained by two mechanisms, one influenced by the nerve terminal and the other independent of innervation.