Rat Fast Muscles Research Articles

Morphometric characteristics of myonuclear distribution in the normal and denervated fast rat muscle fiber

Unlike the majority of mammalian tissues, which have mononuclear cells as a basic unit of the tissue composition, skeletal muscle fiber is a polynuclear syncytium. Polynuclear organization offers an additional possibility for the regulation of protein expression: it can also be controlled at the level of myonuclear distribution and specialization. Distribution of myonuclei can be considered as the distribution of genes. Variability in gene concentration may have important impact on the regional differentiation of the muscle fiber, since it leads to different regional concentrations of various gene products including factors controlling their expression. The aim of the present study was: 1) to provide morphometrical data on the myonuclear distribution in the junctional and extrajunctional regions of the normal fast rat muscle fiber, and 2) to analyze, whether morphomertical parameters of nuclear distribution change after mechanical denervation of this muscle. Single muscle fibers were isolated from the normal and denervated fast rat m. sternomastoideus. Their neuromuscular junctions were stained by thiocholine histochemical procedure and myonuclei were fluorescently labeled by Hoechst 33342. Myonuclear distribution in each individual muscle fiber was morphometrically analyzed on the image analyzer. Synaptic concentrations of myonuclei were found to exceed extrasynaptic concentrations by a factor of 17. The number of myonuclei accumulated at the endplates did not change after one or two weeks of denervation, neither did the morphometric parameters of these nuclei. A higher concentration of myonuclei due to muscle atrophy was observed in the extrasynaptic region and the longitudinal axis of these nuclei also became significantly shorter. Unchanged morphometric parameters of the junctional myonuclei after denervation are indicative of either irreversibility of the nerve-induced formation of nuclear clusters in this region or persistence of the factors responsible for their formation and maintenance.

Early changes in performance, blood flow and capillary fine structure in rat fast muscles induced by electrical stimulation.

1. Muscle blood flow, capillary fine structure and performance were investigated in the early stages of chronic indirect electrical stimulation of ankle flexors in the rat. 2. The fast muscles tibialis anterior (TA), extensor digitorum longus (EDL) and extensor hallucis proprius (EHP) were unilaterally stimulated via the right common peroneal nerve at 10 Hz and supramaximal voltage for 8 h a day for 2, 3 or 7 days and compared with muscles from control animals. 3. Muscle blood flow (MBF) was estimated at rest and during contractions by radioactive microspheres. It was higher at rest than in unstimulated controls only in muscles stimulated for 2 days; during contractions it was higher in some muscles stimulated for 3 days than in controls, and in all muscles by 7 days (192 +/- 17 vs. 149 +/- 12 ml (100 g)-1min-1 in controls). 4. Electron microscopical evaluation of individual capillaries in EHP fixed by superfusion in situ revealed thickening of capillary endothelium and decreased lumen volume in muscles stimulated for 7 (P < 0.005) but not 3 days. Significantly smaller capillary size indicates the presence of newly formed capillaries. 5. Isometric twitch tension, recorded from combined TA and EDL in stimulated and contralateral legs during 5 min contractions at 4 Hz, gradually declined from 175 +/- 9 to 99 +/- 4 kN m-2 after 7 days of stimulation (P < 0.05) while the fatigue index, calculated as (final twitch tension/peak twitch tension) x 100, increased from 69.8 +/- 3.4 to 90 +/- 3.0 % (P < 0. 05). No significant changes in the fatigue index occurred in muscles stimulated for 2 or 3 days. 6. Lower peak tension, but not fatigue index or MBF, was also observed in muscles contralateral to those stimulated for 3 and 7 days, which thus do not represent appropriate controls. 7. We conclude that the high resting blood flow found in muscles stimulated for 2 days may initiate the capillary growth reported previously, while the relatively modest increase in MBF during contractions in muscles that had been stimulated for 7 days may be due to increased capillary supply. Swelling of the capillary endothelium and decreased volume of the capillary lumen may result in an increased proportion of time spent by red blood cells in capillaries, which would improve oxygen extraction.

Increased activity improves recovery of partially denervated fast rat muscles

Partial denervation of the neonatal rat extensor digitorum longus muscles by removing the L4 spinal nerve and thus 80% of its innervation [A.L. Connold, T.J. Fisher, S. Maudarbocus, G. Vrbová, Response of developing fast muscles to partial denervation, Neuroscience 46 (1992) 981–988; F. Tyč, G. Vrbová, The effect of partial denervation of developing rat fast muscles on their motor unit properties, J. Physiol. 482 (1995) 651–660] results in its permanent weakness. The possibility that the weakness that follows partial denervation is due to the effects of reducing activity of the muscle during a critical stage of development was studied here. Partial denervation was carried out in 3-day-old pups by removing the L4 spinal nerve. To enhance motor activity two days later some animals had injections of l-Dopa twice a day for 8 days. This treatment induced locomotor activity for at least 2 h/day. The muscles from treated and untreated animals were examined 2 months later. There was a significantly smaller reduction of weight and force production in the muscles from l-Dopa treated animals. Both twitch and tetanic force developed by the EDL muscle from the treated group was twice that of the control untreated group. This effect was due mainly to the larger size of the motor units (MUs) in the l-Dopa treated muscles compared to the controls. The mean motor unit force in the untreated group was 69% of that in the control muscle, whereas this value was 127% in the l-Dopa treated animals. Thus it appears that the activity induced by treatment with l-Dopa could to some extent prevent the loss of weight and force output seen after partial denervation of young fast muscles.

Acetylcholinesterase mRNA Level and Synaptic Activity in Rat Muscles Depend on Nerve-Induced Pattern of Muscle Activation

Acetylcholinesterase (AChE) mRNA levels are severalfold higher in fast rat muscles compared with slow. We hypothesized that AChE mRNA levels and AChE activity in the neuromuscular junction depend on a specific nerve-induced pattern of motor unit activation. Chronic low-frequency stimulation, mimicking the activation pattern in slow muscles, was applied to fast muscles in rats. Molecular forms of AChE were analyzed by velocity sedimentation, and AChE mRNA levels were analyzed by Northern blots. AChE mRNA levels in stimulated fast muscles dropped to 10-20% of control after 1 week and became comparable to those in slow soleus muscles. The activity of the junctional A12 AChE form in 35 d stimulated fast muscles decreased to 56% of control value, reaching that in the soleus muscle. Therefore, synaptic AChE itself depends on the muscle activation pattern. Complete inactivity after denervation also decreased the AChE mRNA level in fast muscles to <10% in 48 hr. In contrast, profuse fibrillations observed in noninnervated immature regenerating muscles maintain AChE mRNA levels at 80% of that in the innervated fast muscles. If protein synthesis was inhibited by cycloheximide, AChE mRNA levels in 3-d-old regenerating muscle, still containing myoblasts, increased approximately twofold. No significant increase after cycloheximide application was observed either in denervated mature fast muscles or in normal slow muscles. Low AChE mRNA levels observed in those muscles are probably not caused by decreased stability of AChE mRNA as demonstrated in myoblasts.

Dantrolene Sodium Reduces the Enhanced Leakage of Creatine Kinase Caused by Ethanol, Cocaine, and Electrical Stimulation in Isolated Fast and Slow Muscles of Rat

Dantrolene Sodium Reduces the Enhanced Leakage of Creatine Kinase Caused by Ethanol, Cocaine, and Electrical Stimulation in Isolated Fast and Slow Muscles of Rat

Dantrolene Sodium Reduces the Enhanced Leakage of Creatine Kinase Caused by Ethanol, Cocaine, and Electrical Stimulation in Isolated Fast and Slow Muscles of Rat

Binge drinking of alcohol, cocaine overdose, or overexertion can lead to rhabdomyolysis characterized by elevated creatine kinase (CK) and myoglobin in the serum, myoglobinuria, and muscle tenderness. Our previous studies showed that ethanol, cocaine, and electrical stimulation enhanced the leakage of CK from isolated soleus and extensor digitorum longus (EDL) muscles of rat. Dantrolene sodium was reported to reduce the muscle damage and elevated serum CK levels in exercised rats. The present study was aimed at testing whether dantrolene can reduce the enhanced leakage of CK from isolated rat soleus and EDL muscles caused by ethanol, cocaine, and electrical stimulation. After 4-hr incubation in oxygenated physiological solution at 37 degrees C, the mean leakage of CK was 1.56 units/mg of muscle in soleus and 0.89 units/mg in EDL. Ethanol at 0.2% increased the leakage of CK by 47% (p < 0.05) in soleus and by 26% in EDL. Cocaine at 1 mM increased the leakage of CK by 55% (p < 0.05) in soleus and by 27% in EDL. Electrical stimulation at 1 Hz for 4 hr increased the mean leakage of CK by 100% (p < 0.05) in soleus and 127% (p < 0.05) in EDL. Dantrolene sodium reduced the enhanced leakage of CK caused by ethanol, cocaine, and electrical stimulation significantly in soleus and slightly in EDL. Dantrolene may involve myoplasmic free Ca2+ in these beneficial effects as in malignant hyperthermia, and may be useful in the treatment of rhabdomyolysis associated with acute alcoholic myopathy, cocaine overdose, and overexertion.

Fast and slow skeletal muscles express a common basic profile of acetylcholinesterase molecular forms.

Recent evidence suggests that the high content of acetylcholinesterase (AChE) globular form G4, characteristic of fast muscles, is controlled by phasic high-frequency activity performed by these muscles. This indicates that inactive, though still innervated, fast muscles should be devoid of their characteristic G4 pool. 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 first tested this hypothesis by examining 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. Ten days after TTX inactivation, the distributions of AChE molecular forms of both fast extensor digitorum longus (EDL) and plantaris muscles were transformed into ones resembling the slow soleus, the latter showing no significant modifications in its AChE profile. Finally, we investigated the impact of nerve-mediated phasic high-frequency stimulation of TTX-inactivated fast and slow muscles on the content of AChE molecular forms. This stimulation produced a profile of AChE molecular forms similar to that observed in control EDL muscles, indicating that phasic activation counteracted the TTX-induced transformation in the distribution of AChE molecular forms in fast EDL muscles. Together, these results are consistent with the proposal that adult fast 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.

Regenerated rat fast muscle transplanted to the slow muscle bed and innervated by the slow nerve, exhibits an identical myosin heavy chain repertoire to that of the slow muscle

Regenerated rat fast muscle transplanted to the slow muscle bed and innervated by the slow nerve, exhibits an identical myosin heavy chain repertoire to that of the slow muscle

Regenerated rat fast muscle transplanted to the slow muscle bed and innervated by the slow nerve, exhibits an identical myosin heavy chain repertoire to that of the slow muscle.

The hypothesis that the limited adaptive range observed in fast rat muscles in regard to expression of the slow myosin is due to intrinsic properties of their myogenic stem cells was tested by examining myosin heavy chain (MHC) expression in regenerated rat extensor digitorum longus (EDL) and soleus (SOL) muscles. The muscles were injured by bupivacaine, transplanted to the SOL muscle bed and innervated by the SOL nerve. Three months later, muscle fibre types were determined. MHC expression in muscle fibres was demonstrated immunohistochemically and analysed by SDS-glycerol gel electrophoresis. Regenerated EDL transplants became very similar to the control SOL muscles and indistinguishable from the SOL transplants. Slow type 1 fibres predominated and the slow MHC-1 isoform was present in more than 90% of all muscle fibres. It contributed more than 80% of total MHC content in the EDL transplants. About 7% of fibres exhibited MHC-2a and about 7% of fibres coexpressed MHC-1 and MHC-2a. MHC-2x/d contributed about 5-10% of the whole MHCs in regenerated EDL and SOL transplants. The restricted adaptive range of adult rat EDL muscle in regard to the synthesis of MHC-1 is not rooted in muscle progenitor cells; it is probably due to an irreversible maturation-related change switching off the gene for the slow MHC isoform.

Fast-to-slow transformation in stimulated rat muscle.

Several previous studies have failed to demonstrate changes due to chronic stimulation in contractile speed of innervated fast rat muscles, and it has been suggested that the adaptive capacity of skeletal muscle in this species is limited. We have reassessed this contention. Fast muscles of the rat hind limb were stimulated continuously at 10 or 20 Hz for 55-61 days. The maximum shortening velocity of the extensor digitorum longus muscles was reduced to 50% of the control value. The proportion of type 1 fibers increased from 4% in control muscle to 34% in stimulated muscles and there was a corresponding reduction in type 2B/D fibers. The proportion of type 2A fibers after stimulation was similar to that in control muscles. These results, taken together with our published analyses of myosin isoform composition of these muscles, show that the mechanisms that control gene expression in response to activity are not exclusive to larger mammals.

Effect of cross-reinnervation on the expression of GLUT-4 and GLUT-1 in slow and fast rat muscles.

We determined whether the twitch-velocity phenotype or the metabolic phenotype of a muscle influences the content of GLUT-4 and GLUT-1 proteins. The soleus (Sol) and extensor digitorum longus (EDL) muscles were cross-reinnervated (X-Sol, X-EDL). After 3 mo the X-EDL had become enriched in slow-twitch oxidative (SO) fibers (70.5% SO) compared with its control (3.8% SO), whereas the X-Sol became enriched in fast-twitch oxidative-glycolytic (FOG) fibers (78.6% FOG) compared with its control (10% FOG). Thus the twitch phenotype of X-Sol shifted to fast-twitch muscle, whereas X-EDL shifted to a slow-twitch muscle. In the X-EDL, the oxidative nature of the X-EDL was increased to 97% oxidative fibers compared with 43% oxidative fibers in the normal EDL. In the Sol the oxidative nature of the X-Sol was retained at 100%. GLUT-4 content was increased 1.6-fold in the X-EDL (P < 0.05) but was not changed in the X-Sol (P > 0.05). GLUT-1 content was increased fourfold in X-EDL but was not altered in the X-Sol. We conclude that GLUT-4 and GLUT-1 content in muscle is related to the oxidative phenotype of the muscle rather than the twitch-velocity phenotype.

Culturing satellite cells from living single muscle fiber explants

Conventional methods for isolating myogenic (satellite) cells are inadequate when only small quantities of muscle, the tissue in which satellite cells reside, are available. We have developed a tissue culture system that reliably permits isolation of intact, living, single muscle fibers with associated satellite cells from predominantly fast and slow muscles of rat and mouse; maintenance of the isolated fibers in vitro; dissociation, proliferation, and differentiation of satellite cells from each fiber; and removal of the fiber from culture for analysis.

The effect of partial denervation of developing rat fast muscles on their motor unit properties

The Journal of PhysiologyVolume 484, Issue 3 p. 811-811 ErrataFree Access The effect of partial denervation of developing rat fast muscles on their motor unit properties First published: 01 May 1995 https://doi.org/10.1113/jphysiol.1995.sp020707AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume484, Issue3May 1, 1995Pages 811-811 RelatedInformation

Effect of alcohol and electrical stimulation on leakage of creatine kinase from isolated fast and slow muscles of rat.

Binge drinking of alcohol may lead to acute alcoholic myopathy with rhabdomyolysis, which is characterized by skeletal muscle damage, elevated serum creatine kinase (CK), and myoglobinuria. This study was undertaken to test whether alcohol acts directly on the skeletal muscles to enhance the leakage of CK, and to assess the influence of fiber-type composition and repetitive contractions of the muscle on the effect of alcohol. After 4 hr of incubation in normal physiological solution at 37 degrees C, mean leakage of CK was 0.7 units/mg from isolated rat extensor digitorum longus (EDL), which has more fast-twitch glycolytic muscle fibers, and 1.2 units/mg from the soleus, which has more slow-twitch oxidative muscle fibers. Ethanol at 0.1, 0.2, and 0.5% concentrations caused significantly greater increase in leakage of CK from soleus than from EDL. In normal physiological solution, electrical stimulation at 1 Hz for 4 hr increased the leakage of CK by about the same degree in both EDL and soleus. In the presence of 0.1 and 0.2% ethanol, electrical stimulation markedly potentiated the alcohol-induced leakage of CK from both soleus and EDL. These results indicate that alcohol increases the leakage of CK by acting directly on skeletal muscle fibers, especially of the slow-twitch oxidative type, and that repeated muscle contractions potentiate the alcohol effect. These studies suggest that exercise may increase the chances of rhabdomyolysis in the alcoholics.

Satellite cells in slow and fast rat muscles differ in respect to acetylcholinesterase regulation mechanisms they convey to their descendant myofibers during regeneration

The hypothesis of satellite cell diversity in slow and fast mammalian muscles was tested by examining acetylcholinesterase (AChE) regulation in muscles regenerating 1) under conditions of muscle disuse (tenotomy, leg immobilization) in which the pattern of neural stimulation is changed, and 2) after cross-transplantation when the regenerating muscle develops under a foreign neural stimulation pattern. Soleus (SOL) and extensor digitorum longus (EDL) muscles of the rat were allowed to regenerate after ischemic-toxic injury either in their own sites or had been cross-transplanted to the site of the other muscle. Molecular forms of AChE in regenerating muscles were analyzed by velocity sedimentation in linear sucrose gradients. Neither tenotomy nor limb immobilization significantly affected the characteristic pattern of AChE molecular forms in regenerating SOL muscles, suggesting that the neural stimulation pattern is probably not decisive for its induction. During an early phase of regeneration, the general pattern of AChE molecular forms in the cross-transplanted regenerating muscle was predominantly determined by the type of its muscle of origin, and much less by the innervating nerve which exerted only a modest modifying effect. However, alkali-resistant myofibrillar ATPase activity on which the separation of muscle fibers into type I and type II is based, was determined predominantly by the motor nerve innervating the regenerating muscle. Mature regenerated EDL muscles (13 weeks after injury) which had been innervated by the SOL nerve became virtually indistinguishable from the SOL muscles in regard to their pattern of AChE molecular forms. However, AChE patterns of mature regenerated SOL muscles that had been innervated by the EDL nerve still displayed some features of the SOL pattern. In regard to AChE regulation, muscle satellite cells from slow or fast rat muscles convey to their descendant myotubes the information shifting their initial development in the direction of either slow or fast muscle, respectively. The satellite cells in fast or slow muscles are, therefore, intrinsically different. Intrinsic information is expressed mostly during an early phase of regeneration whereas later on the regulatory influence of the motor nerve more or less predominates.

Effect of physostigmine and exercise on choline acetyltransferase and acetylcholinesterase activities in fast and slow muscles of rat

The interaction of physostigmine (Phy) and exercise on cholineacetyltransferase (ChAT) and acetylcholinesterase (AChE) have been studied in the fast extensor digitorum longus (EDL) and slow soleus muscles of rat. ChAT decreased significantly by trained exercise in EDL muscle and Phy prolonged this effect even up to 24 h. Soleus muscles showed a small increase of ChAT due to exercise but Phy + exercise did not change significantly. Both EDL and soleus showed a marked decrease in AChE activity due to subacute administration of Phy + trained exercise, exhibiting an additive effect. No recovery was observed in ChAT and AChE activities of EDL even after 24 h in Phy + trained exercise group. Our results suggest that Phy and exercise has significant effect on the synthetic (ChAT) and degradative (AChE) enzymes of acetylcholine in active EDL muscle. Exercise has prolonged the inhibitory effect of Phy on ChAT and AChE activities both in active EDL and passive soleus muscles. This study showed that Phy + exercise modified the functional activity of cholinergic system in EDL and soleus muscles.

Effect of cocaine on leakage of creatine kinase from isolated fast and slow muscles of rat

Since patients with cocaine overdose were reported to develop rhabdomyolysis involving skeletal muscle damage leading to elevated levels of serum creatine kinase (CK), we determined whether cocaine can directly act on isolated rat skeletal muscles and increase the leakage of CK. In the fast-twitch muscle such as the extensor digitorum longus (EDL), following exposure to normal physiological solution for 1, 2, 3, and 4 hr, the mean leakage of CK was 0.6, 0.7, 0.9, and 1.2 units/mg of muscle respectively. On exposure of EDL to 0.1, 0.5, and 1.0 mM cocaine, there was no significant change in CK leakage. In the slow-twitch muscle such as the soleus, following exposure to normal physiological solution for 1, 2, 3, and 4 hr, the mean leakage of CK was 1.5, 2.2, 2.7, and 3.1 units/mg, which was significantly greater (P<0.001) than in EDL at each time interval. On exposure of soleus to 0.1 mM cocaine, the CK leakage did not increase significantly, but on exposure to 0.5 mM cocaine, it significantly increased to 2.4, 3.4, 4.4, and 5.7 units/mg, and on exposure to 1.0 mM cocaine, it further increased to 2.7, 4.9, 6.5, and 7.6 units/mg. The CK activity of fresh muscle homogenate was 115.5 units/mg in EDL and 51.9 units/mg in soleus. These results indicate that cocaine can directly act on skeletal muscle and increase the leakage of CK especially from slow-twitch muscle like soleus, but not from fast-twitch muscle like EDL.

Response of developing rat fast muscles to partial denervation

The changes of motor unit size following partial denervation of the extensor digitorum longus muscles in rat neonates (at five to six days) and later in development (at 18–20 days) were studied. Extensor digitorum longus muscle is innervated mainly by axons from L4 ventrat ramus and to a lesser extent by axons from L5 ventrat ramus. In neonates the motor units in extensor digitorum longus are large, and they become restricted to their adult size during the first two weeks of life. Six to 10 weeks after removing the major input to extensor digitorum longus, i.e. L4 ventrat ramus at five to six days, the motor unit sizes of axons in the remaining L5 ventrat ramus decrease from their expanded neonatal territory to their adult smaller size. In spite of partial denervation the motor units remain small throughout the animal's life and the denervated muscle fibres do not become “occupied” by sprouts from the remaining axons of L5 ventrat ramus motor nerves. Partial denervation of extensor digitorum longus muscles at 18–20 days by section of the L4 ventrat ramus leads to the expected two- to three-fold increase in the size of motor units of L5 ventrat ramus. These results are taken to show that fast motor units of neonatal rats are unable to maintain their enlarged peripherat field, while later in development their axons can sprout and occupy an expanded peripherat field.

Changes produced by increased hydrostatic pressure in isometric contractions of rat fast muscle.

1. Muscle fibre bundles isolated from the extensor digitorum longus (a fast muscle) of the rat were exposed to different hydrostatic pressures (range 0.1-10 MPa), in order to determine the pressure dependence of their isometric contractions. 2. The pressure dependent changes in the contractions were reversible and linearly related to pressure. 3. The peak tension, the time to peak and the time to half-relaxation of a twitch contraction increased with pressure; the mean (+/- S.E.M.) percentage increases were 5.9 +/- 0.5% MPa-1, 2.7 +/- 0.2% MPa-1 and 2.7 +/- 0.4% MPa-1, respectively. 4. In a fused tetanus, the tension was typically depressed at high pressure (0.9 +/- 0.16% MPa-1); the half-time of tension rise was decreased (2.1 +/- 0.2% MPa-1) and the half-time of exponential relaxation was increased (2.4 +/- 0.3% MPa-1).

Influence of innervation on molecular forms of acetylcholinesterase in regenerating fast and slow skeletal muscles

Nerve-intact muscle regenerates were prepared by ischemic-toxic injury of slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles of the rat. Rapid innervation of regenerating myotubes modified intrinsic patterns of AChE molecular forms, revealed by velocity sedimentation in linear sucrose gradients. Regarding their onset, the effects of innervation can be classified as early and late. The earliest changes in the SOL regenerates appeared a few days after innervation by their motoneurons: the activity of the 13 S AChE form (A 8) increased significantly in comparison to non-innervated regenerates. The pattern of AChE molecular forms became similar to that in the normal SOL muscle during the 2nd week after injury. In contrast, no major differences were observed between 8 day-old innervated and non-innervated EDL regenerates. Their patterns of AChE molecular forms resembled that in the normal EDL. However, the predominance of the 10 S AChE form (G 4) characteristic for the 2-week old non-innervated regenerates was prevented by innervation. Early effect of innervation observed in the SOL regenerates but not in the EDL may be due to intrinsically different response of the regenerating SOL myotubes to innervation. Rather high extrajunctional activity of the asymmetric 16 S (A 12) molecular form of AChE in early regenerates was reduced to adult level in about 3 weeks in the SOL, and nearly completely suppressed in 5 weeks after innervation in the EDL regenerates. This reduction is assumed to be a late effect of innervation, as well as a decrease of the activity of the 4 S AChE form (G 1) in the SOL regenerates. A suppressive mechanism is activated in the extra-junctional regions of the innervated muscle regenerates during their maturation.(ABSTRACT TRUNCATED AT 250 WORDS)