Botulinum-induced muscle paralysis alters metabolic gene expression and fatigue recovery.
We evaluated the physiological, histochemical, and biochemical consequences of inhibiting contractile activity in rat skeletal muscles with botulinum toxin A (BTX). Contractile activity was entirely eliminated 12-18 h after a single, focal, intramuscular injection of BTX into the rat tibialis anterior muscle (TA). Neuromuscular transmission remained completely inhibited for 10-12 days, then slowly recovered. BTX-treated muscles exhibited a lower resistance to both high- and low-frequency fatigue at 7 and 14 days after injection, but contractile force recovered more rapidly in treated TA after fatigue. Treated TA showed a twofold increase in the activity of the triglyceride hydrolase enzyme lipoprotein lipase (LPL) and a comparable increase in the relative abundance of LPL steady-state mRNA. In contrast, there was a 28% reduction in protein levels of the muscle isozyme of glycogen phosphorylase (MGP) and a 70% decrease in relative MGP transcript levels. Similar changes in relative transcript levels of LPL and MGP were observed in the predominantly fast-twitch extensor digitorum longus after BTX injection, but relative LPL and MGP mRNA levels were not altered in predominantly slow-twitch soleus. Histochemical evidence indicated that fast-twitch glycolytic fibers had increased lipid content. These biochemical alterations were reversed 120 days after BTX treatment despite persistent atrophy.
Gorin
F
F
Department of Neurology, School of Medicine, University of California, Davis 95616, USA. fagarin@ucdavis.edu
Herrick
K
K
Froman
B
B
Palmer
W
W
Tait
R
R
Carlsen
R
R
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006614:Hindlimb; D006651:Histocytochemistry; D007527:Isoenzymes / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D018763:Muscle Fatigue / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D010243:Paralysis / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology*; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic
D007527:Isoenzymes; D009466:Neuromuscular Blocking Agents; D006005:Phosphorylases; D008071:Lipoprotein Lipase; D001905:Botulinum Toxins