Fast and slow skeletal muscles express a common basic profile of
acetylcholinesterase molecular forms .
Boudreau-Larivi[grave]ere, C[acute]eline, Victor Gisiger, Robin N.
Michel, Douglas A. Hubatsch, and Bernard J. Jasmin.
Department of Physiology, Faculty of Medicine, University of
Ottawa, Ottawa, Ontario, Canada K1H 8M5, D[acute]epartement
d'Anatomie, Facult[acute]e de M[acute]edecine, Universit[acute]e de
Montr[acute]eal, Montr[acute]eal, Qu[acute]ebec, Canada H3C 3J7
APStracts 3:0123C, 1996.
Acetylcholinesterase (AChE) exists as a family of molecular forms
whose expression in skeletal muscles is modulated by the levels of
superimposed neuronal activation. Recent evidence has led to the
proposal that the high content of the globular form G4 characteristic
of fast muscles, is tightly controlled by phasic high-frequency
activity performed by these muscles. This suggests that inactive,
although still innervated fast muscles should be devoid of their
characteristic G4 pool and, therefore, should only contain a minimal
amount of tetramer similar to that present in active slow-twitch
muscles. Accordingly, in the absence of phasic activity both fast and
slow muscles should exhibit a common basic profile of AChE molecular
forms of the slow type. We tested this hypothesis by using three
distinct, yet complementary approaches. First, we examined the AChE
content in cultures of myotubes obtained from the fusion of satellite
cells originating from fast and slow muscles. These two cell
populations produced AChE molecular form profiles of the slow type
characterized by modest levels of G4 together with an increased
proportion of the asymmetric forms A8 relative to A12. Second, we
determined the impact of muscle paralysis on the specific content of
AChE molecular forms of adult rat fast and slow muscles. Complete
paralysis of hindlimb muscles was achieved by chronic superfusion of
tetrodotoxin (TTX) onto the sciatic nerve. Five to 10 days following
TTX-inactivation, the distributions of AChE molecular forms of both
fast EDL and plantaris muscles were transformed into ones resembling
the slow soleus, the latter showing no significant modifications in
its AChE profile. These AChE distributions were clearly distinct from
those observed following denervation. Finally, we investigated the
impact of nerve-mediated stimulation of TTX-inactivated fast and slow
muscles on the content of AChE molecular forms. Hindlimb muscle
contractile activity was elicited by stimulating the sciatic nerve
distal to the site of TTX delivery with a pattern mimicking phasic
high-frequency activation of fast muscles (100 Hz bursts, 1 sec
duration every 2 min, 1 hr daily, 7 days starting 24 hr after
initiation of TTX-inactivation). In stimulated TTX-inactivated EDL
muscles, levels of G4 were significantly higher (89%; P < 0.05)
whereas those of A8 were reduced (32%; P < 0.05) in comparison
to TTX-inactivated muscles. The stimulation produced a profile of
AChE molecular forms similar to that observed in control EDL muscle
indicating that phasic activation counteracted the TTX-induced
transformation in the distribution of AChE molecular forms in fast
EDL muscle. Together, these results are consistent with the proposal
that adult fast skeletal muscles constitutively express a basic
profile of AChE molecular forms of the type displayed by slow
muscles, onto which varying levels of G4 are added according to the
amount of phasic activity performed by the muscles.
Received 28 September 1995; accepted in final form 3 April 1996.
APS Manuscript Number C596-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 23 April 96