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Regulation of turnover and number of acetylcholine receptors at neuromuscular junctions
No full textThe number and metabolic stability of acetylcholine receptors (AChRs) at neuromuscular junctions of rat tibialis anterior (TA) and soleus (SOL) muscles were examined after denervation, paralysis by continuous application of tetrodotoxin to the nerve, or denervation and direct stimulation of the muscle through implanted electrodes. After 18 days of denervation AChR half-life declined from about 10 days to 2.3 days (TA) or 3.6 days (SOL) and after 18 days of nerve conduction block to 3.1 days (TA). In contrast, the total number of AChRs per endplate was unaffected by these treatments. Denervation for 33 days had no further effect on AChR half-life but reduced the total number of AChRs to about 54% (SOL) or 38% (TA) of normal. Direct stimulation of the 33-day denervated SOL from day 18 restored normal AChR stability and counteracted muscle atrophy but had no effect on the decline in AChR number. The results indicate that motoneurons control the stability of junctional AChRs through evoked muscle activity and the number of junctional AChRs through trophic factors
Expression of myosin heavy chain isoforms in stimulated fast and slow rat muscles.
Full text linkThe expression of 4 myosin heavy chain (MHC) isoforms was analyzed in the rat soleus (SOL) and extensor digitorum longus (EDL) muscles after denervation and chronic electric stimulation. The stimulation frequencies used were 20 and 150 Hz and the amount of stimulation was either large (20 Hz), intermediate (150 Hz), or small (150 Hz). These patterns resemble some features of normal motor unit activity in SOL and EDL of freely moving rats (Hennig and Lømo, 1985). The relative expression of each MHC isoform depended strongly on the stimulation pattern. Furthermore, for any particular stimulation pattern, fibers in SOL and EDL expressed different MHCs. Coexistence of different MHC types in the same fiber was frequently observed in stimulated muscles. 20-Hz stimulation preserved normal expression of type 1-MHC in SOL but failed to induce type 1-MHC in type 2 fibers of the EDL, where type 2A- and 2X-MHC expression dominated and type 2B-MHC expression was completely suppressed. 150-Hz low-amount stimulation preserved nearly normal 2B-MHC expression in many type 2 fibers of the EDL but failed to induce type 2B-MHC expression in the SOL, where 2X-MHC became predominant. 150-Hz high-amount stimulation differed from 150-Hz small amount stimulation by suppressing almost all type 2B-MHC expression in EDL and by inducing considerable type 2A-MHC expression in the SOL. Scattered fibers in EDL that were probably the original type 1 fibers responded differently from both type 2 fibers in the EDL and from type 1 fibers in the SOL to stimulation
Effects of chronic nerve conduction block on formation of neuromuscular junctions and junctional AChE in the rat
No full textEffects of chronic nerve conduction block on formation of neuromuscular junctions and junctional AChE in the rat
No full textThe development of ectopic n.m.j.s. between the transplanted superficial fibular nerve and the soleus muscle has been studied in adult rats. Impulse conduction in the sciatic nerve was blocked chronically and synapse formation between the blocked fibular nerve and the paralysed soleus was compared with synapse formation between non-blocked fibular nerves and denervated soleus muscles. Nerves with conduction block readily made new n.m.j.s. Thus 6 and 10--14 days after the onset of the block the number of newly innervated muscle fibres, the percentage of innervated fibres responding with action potentials and the frequency of m.e.p.p.s. at new junctions were comparable to that observed during innervation by non-blocked nerves. Muscle fibres innervated by both the original soleus nerve and the foreign fibular nerve were regularly encountered in the impulse blocked preparations. Junctions formed by impulse blocked fibular nerves had either no or very little AChE activity 10--15 days after the onset of the block. The evidence for this was 1) weak staining for CHE; 2) prolonged rise time and 1/2 decay time of m.e.p.p.s; 3) positive correlation between m.e.p.p. amplitude and 1/2 decay time and 4) insensitivity to anticholinesterases. In contrast, junctions formed by non-blocked fibular nerves had strong AChE activity by these criteria at corresponding times. AChE activity at the original soleus endplates was much reduced 10--15 days after the onset of conduction block
Slow to fast transformation of denervated soleus muscles by chronic high frequency stimulation in the rat.
No full text1. Adult soleus muscles were denervated and stimulated directly for 2-130 days
with 'fast' (short pulse trains at 100 Hz) or 'slow' (continuously at 10 Hz, or
long pulse trains at 15 Hz) stimulus patterns. 2. At the end of the period of
stimulation isometric twitches and tetani and isotonic shortening velocities were
measured. Frozen cross-sections were later examined with antibodies against
myosin heavy chains specific for adult fast, adult slow and fetal myosin. 3.
Isometric twitch duration (twitch time-to-peak and half-relaxation time)
decreased during intermittent 100 Hz stimulation to values that were almost as
fast as in the normal extensor digitorum longus (EDL) (95 and 94%
transformation). The major part of the decrease occurred between 2 and 21 days
after the onset of stimulation, and was accompanied by post-tetanic potentiation
of the twitch, 'sag' in tension during an unfused tetanus, lower twitch/tetanus
ratio and marked shifts to the right (higher frequencies) of the
tension-frequency curve of the muscle. In contrast, during 10 or 15 Hz
stimulation the isometric twitch duration remained slow, the twitch continued to
show post-tetanic depression and absence of 'sag', while the twitch/tetanus ratio
increased. 4. Denervation per se led to a slight increase and, then, after about
a month, to a moderate and gradual decrease in twitch duration. The
twitch/tetanus ratio increased markedly and post-tetanic depression became less
pronounced or disappeared. Muscle weight and particularly tetanic tension were
markedly reduced and these reductions were to a large extent counteracted by
electrical stimulation. 5. Implantation of sham electrodes had no effect on
twitch duration of denervated or innervated control muscles, but reduced tetanic
tension in the innervated control muscles. 6. Maximum isotonic shortening
velocity of the whole muscle (mm/s) increased during intermittent 100 Hz
stimulation to a value as fast as in the normal EDL (110% transformation). Since
the muscle fibres also increased in length (35%) maximum intrinsic shortening
velocity (fibre lengths/s) was only incompletely transformed (55%). The increase
in Vmax occurred between 7 and 14 days after the onset of stimulation. 7. All the
fibres stimulated intermittently at 100 Hz were strongly labelled with anti-fast
myosin and more than 90% were in addition weakly labelled by anti-slow myosin.
Weak and variable labelling with anti-fast myosin was first detected 7 days after
the onset of stimulation. In contrast, essentially all the fibres stimulated at
10 or 15 Hz showed no binding of anti-fast but strong binding of anti-slow
myosin.(ABSTRACT TRUNCATED AT 400 WORDS
Three myosin heavy chain isoforms in type 2 skeletal muscle fibers.
Full text linkMammalian skeletal muscles consist of three main fibre types, type 1,2A and 2B
fibres, with different myosin heavy chain (MHC) composition. We have now
identified another fibre type, called type 2X fibre, characterized by a specific
MHC isoform. Type 2X fibres, which are widely distributed in rat skeletal
muscles, can be distinguished from 2A and 2B fibres by histochemical ATPase
activity and by their unique staining pattern with seven anti-MHC monoclonal
antibodies. The existence of the 2X-MHC isoform was confirmed by immunoblotting
analysis using muscles containing 2X fibres as a major component, such as the
normal and hyperthyroid diaphragm, and the soleus muscle after high frequency
chronic stimulation. 2X-MHC contains one determinant common to 2B-MHC and another
common to all type 2-MHCs, but lacks epitopes specific for 2A- and 2B-MHCs, as
well as an epitope present on all other MHCs. By SDS-polyacrylamide gel
electrophoresis 2X-MHC shows a lower mobility compared to 2B-MHC and appears to
comigrate with 2A-MHC. Muscles containing predominantly 2X-MHC display a velocity
of shortening intermediate between that of slow muscles and that of fast muscles
composed predominantly of 2B fibres
Myosin heavy chain isoforms and velocity of shortening of type 2 skeletal muscle fibres.
No full textRas is involved in nerve-activity-dependent regulation of muscle genes
No full textGene expression in skeletal muscle is regulated by the firing pattern of motor neurons, but the signalling systems involved in excitation-transcription coupling are unknown. Here, using in vivo transfection in regenerating muscle, we show that constitutively active Ras and a Ras mutant that selectively activates the MAPK(ERK) pathway are able to mimic the effects of slow motor neurons on expression of myosin genes. Conversely, the effect of slow motor neurons is inhibited by a dominant-negative Ras mutant. MAPK(ERK) activity is increased by innervation and by low-frequency electrical stimulation. These results indicate that Ras-MAPK signalling is involved in promoting nerve-activity-dependent differentiation of slow muscle fibres in vivo
Signaling pathways involved in the control of fibre type specification and fibre size induced by nerve activity
No full textEmbryonic and neonatal myosin heavy chain in denervated and paralyzed rat skeletal muscle
No full textUsing immunofluorescence procedures with specific polyclonal and monoclonal
antimyosin antibodies we have found that embryonic and neonatal myosin heavy
chains (MHCs), which in rat skeletal muscle disappear during the first weeks
after birth, are reexpressed in adult muscle after denervation. Reactivity for
embryonic and neonatal MHCs was detected in some fibers as early as 3 days after
denervation, became more evident by 7 days, and occurred exclusively in the type 2A fiber population. Paralysis of innervated muscles by tetrodotoxin block of the sciatic nerve also resulted in the reappearance of embryonic and neonatal MHCs in type 2A fibers. Significant variation in the degree of immunoreactivity was observed in different segments of the same muscle fiber, suggesting that coordination of muscle fiber nuclei in the control of myosin heavy chain gene expression is partially lost following denervation
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