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Expression and distribution of sodium channels in short‐ and long‐term denervated rodent skeletal muscles.
Author(s) -
Lupa M T,
Krzemien D M,
Schaller K L,
Caldwell J H
Publication year - 1995
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1995.sp020571
Subject(s) - rodent , term (time) , distribution (mathematics) , sodium channel , skeletal muscle , rodent model , neuroscience , sodium , biology , chemistry , microbiology and biotechnology , biophysics , medicine , endocrinology , ecology , physics , mathematics , organic chemistry , mathematical analysis , quantum mechanics
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.