Botulinum-induced muscle paralysis alters metabolic gene expression
and fatigue recovery .
Gorin, Fredric, Kevin Herrick, Byron Froman, Warren Palmer, Robert
Tait, and Richard Carlsen.
Department of Neurology, School of Medicine University of
California, Davis, California, 95616, Department of Pediatrics,
School of Medicine University of Colorado Health Sciences Center,
Denver, Colorado, 80262, Department of Human Physiology, School of
Medicine University of California, Davis, California, 95616, Exercise
Research Division, School of Kinesiology, University of Illinois,
Chicago, Illinois 60680
APStracts 2:0228R, 1995.
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 hours 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
following injection, but contractile force recovered more rapidly in
treated TA following fatigue. Treated TA showed a 2-fold 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 (EDL) 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 (FG) fibers had increased lipid content.
These biochemical alterations were reversed 120 days after Btx
treatment despite persistent atrophy.
Received 20 March 1995; accepted in final form 27 July 1995.
APS Manuscript Number R189-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.