Biomedical subjects

T Lømo

Publications and source records attributed to T Lømo.

At least 37 records · Page 2Linked to original sources

PubMed1994

Factors causing different properties at neuromuscular junctions in fast and slow rat skeletal muscles.

Neuromuscular junctions on fast and slow skeletal muscle fibers have different properties. Possible reasons for these differences were examined in adult rat soleus (SOL) muscle fibers reinnervated at new ectopic or old denervated sites by fast fibular (FIB) or slow SOL motoneurons. FIB motoneurons formed large ectopic junctions with a high density of nerve terminal varicosities (fast appearance), whereas SOL motoneurons formed small ectopic junctions with a low density of varicosities (slow appearance). Both FIB and SOL motoneurons formed small junctions with a slow appearance when reinnervating old SOL endplates. FIB nerves innervating ectopic sites and SOL nerves reinnervating old sites had the same appearance whether they contacted the SOL fibers alone (single innervation) or together (dual innervation). Continuous stimulation of the FIB nerve at 10 Hz for 3-4 months reduced the size of ectopic FIB and intact extensor digitorum longus (EDL) junctions and caused a modest reduction in density of terminal varicosities in EDL. Junction size and muscle fiber diameter were positively correlated, but the slope describing this relation was steeper for FIB junctions than for SOL junctions. It is concluded that in the present system (1) motoneuron type and not muscle fiber type determines the fast or slow character of the neuromuscular junction. (2) denervated endplates of one type place stable and severe constraints on the termination pattern of reinnervating axons of another type, (3) the appearance of fast EDL junctions undergoes a modest fast to slow transformation when exposed to long-term slow pattern stimulation, and (4) not only the size of the muscle fibers, but also the type and firing pattern of the motoneurons and the spatial constraints at preformed endplates influence the relation between junction size and muscle fiber diameter.

Animals↗

PubMed1993

Changes in K+, Na+ and calcium contents during in vivo stimulation of rat skeletal muscle.

The effects of in vivo stimulation via the sciatic nerve on Na+, K+ and calcium contents in slow-twitch and fast-twitch muscles were compared. Whereas intermittent stimulation for 24 h at 20 Hz caused only minor changes in soleus (SOL), a considerable loss of K+ (around 24%) and gain of Na+ (around 84%) was observed in extensor digitorum longus (EDL) and tibialis anterior (TA) muscles. These changes could be detected within 0.5 h and a plateau was maintained from 2 to 24 h. Total calcium content increased progressively, reaching values 245 and 382% above the control level in EDL and TA muscle, respectively, after 24 h of 20 Hz stimulation. Whereas the Na+ and K+ content recovered within a few hours, calcium content did not return towards control level until after 48 h of rest. In a pilot study performed with continuous stimulation at 10 Hz, the changes in Na+ and K+ contents in SOL, EDL and TA muscle were comparable to those at 20 Hz. The concentration of the Na(+)-K+ pumps was highest in the fast-twitch EDL and TA muscles and was unaffected by 10 Hz stimulation. It is concluded that a stimulation pattern leading to a rise in intracellular Na+ and a loss of K+ may cause a marked accumulation of calcium. These events seem to be related to insufficient activation of the Na-K+ pump rather than to variations in the total Na(+)-K+ pump capacity.

Adenosine Triphosphate↗

PubMed1993

Degradation of two AChR populations at rat neuromuscular junctions: regulation in vivo by electrical stimulation.

The effect of electrical stimulation on the stability of junctional ACh receptors (AChR) on soleus muscles of Wistar rats was compared to that of denervation and reinnervation. Denervation causes the degradation rate of the slowly degrading AChRs (Rs) at the neuromuscular junction to accelerate and be replaced by rapidly degrading AChRs (Rr), while reinnervation restabilizes the accelerated Rs. Electrical stimulation initiated at the time of denervation prevented the acceleration of the Rs. It could not, however, reverse the effect of denervation if initiated after the AChRs became destabilized, nor could it slow the degradation rate of the Rr. We conclude that electrical stimulation of denervated muscle downregulates the expression of the Rr and prevents the destabilization of Rs.

Animals↗

PubMed1990

Regulation of turnover and number of acetylcholine receptors at neuromuscular junctions.

The 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.

Acetylcholine↗

PubMed1990

Expression of myosin heavy chain isoforms in stimulated fast and slow rat muscles.

The 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Three myosin heavy chain isoforms in type 2 skeletal muscle fibres.

Mammalian 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.

Animals↗

PubMed1989

Long-term effects of altered activity on skeletal muscle.

This paper is a brief summary of some results obtained by stimulating denervated rat soleus (SOL) and extensor digitorum longus (EDL) muscles in vivo with different patterns of stimuli. It is concluded (1) that appropriate stimulation can maintain and restore normal properties in extrajunctional regions of denervated muscle; (2) that SOL and EDL respond differently to identical stimulation, indicating that the two muscles are intrinsically different; (3) that both frequency and amount of stimulation influence contractile properties but to varying degrees depending on the property and on the type of muscle under study; and (4) that the effects of stimulation on isometric and isotonic speed of shortening can be partly accounted for by its effect on excitation-contraction coupling processes and myosin heavy chain (MHC) expression.

Animals↗

PubMed1988

Embryonic and neonatal myosin heavy chain in denervated and paralyzed rat skeletal muscle.

Using 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.

Aging↗

PubMed1988

Control of number and distribution of synapses during ectopic synapse formation in adult rat soleus muscles.

Changes in the number and distribution of synaptic inputs and acetylcholine receptor clusters were studied during the formation of ectopic nerve-muscle junctions between the transplanted fibular nerve and the denervated soleus muscle of adult rats. The tibial nerve was cut 3 weeks after implanting the fibular nerve. New sites of transmission were first detected 3 days after the cut. These sites were located electrophysiologically, marked by dye and found to coincide with clusters of acetylcholine receptors. There were no ectopic clusters away from fibular nerve sprouts and no clusters on muscles which had not been denervated. Three days after cutting the tibial nerve, the acetylcholine receptor clusters, and probably also the sites of transmission, were randomly distributed along individual muscle fibres. Six days after the cut, the clusters continued to be randomly distributed whereas the synaptic inputs were either close together (within 300 microns) or more than 600 microns apart. Two weeks later the spatial distributions of both clusters and inputs were similar with peaks around 100-300 microns, 1200-1400 microns and 2000-2600 microns. No ectopic clusters were closer than 0.5 mm to the original endplate. We conclude that nerve-muscle contacts and associated acetylcholine receptor clusters initially form at random. One or a few of these contacts develop further and, as a result, the surrounding regions undergo changes that prevent the contacts initially formed there from being maintained. Apparently, in this preparation, approximately 1.5 mm length of fibre is needed to support the maturation and maintenance of each ectopic endplate (mean length 111 micron).

Animals↗

PubMed1988

Fibre types, calcium-sequestering proteins and metabolic enzymes in denervated and chronically stimulated muscles of the rat.

1. Fibre types, Ca2+-sequestering proteins (parvalbumin, sarcoplasmic reticulum Ca2+-ATPase), enzyme activities of energy metabolism, and lactate dehydrogenase isozymes were studied in extensor digitorum longus (EDL) and soleus muscles of adult rats after denervation and direct stimulation for 45-61 days. The stimulation resembled the firing patterns of normal motor units (Hennig & Lømo, 1985) in either soleus (20 Hz, high amount) or EDL (150 Hz, low and high amount). 2. Low- and high-amount 150 Hz stimulation maintained essentially normal properties in the denervated EDL and induced many EDL-like properties in the denervated soleus, e.g. pronounced increases in Ca2+-ATPase and parvalbumin contents, a rise in the glycolytic enzyme activities, as well as a reversal of the lactate dehydrogenase H/M subunit ratio. The 150 Hz high-amount stimulation was not as efficient as the 150 Hz low amount in maintaining the fast properties of denervated EDL with the exception of the enzymes of aerobic oxidative metabolism. High-amount 20 Hz stimulation maintained essentially normal properties in the soleus but induced only moderate slow muscle characteristics in the EDL. 3. The maintenance of essentially normal properties by 'native' and the changes induced by 'foreign' stimulus patterns in the absence of the nerve indicate that evoked muscle activity plays a major role in controlling the phenotypic expression of muscle properties. However, the different responses of the denervated fast- and slow-twitch muscles to identical stimulus patterns further suggest that rat EDL and soleus muscles contain intrinsically different muscle fibres.

Animals↗

PubMed1988

Slow-to-fast transformation of denervated soleus muscles by chronic high-frequency stimulation in the rat.

1. 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)

Action Potentials↗

PubMed1988

Control of contractile properties within adaptive ranges by patterns of impulse activity in the rat.

These experiments explore the relationship between patterned impulse activity and contractile properties of skeletal muscles. Soleus (SOL) and extensor digitorum longus (EDL) muscles of adult rats were denervated and stimulated directly from 4 to 15 weeks with the same number of pulse trains at different intratrain pulse frequencies (1-500 Hz), with different numbers of pulse trains (864-4,320,000 pulses/d) at the same intratrain pulse frequencies, or with different combinations of pulse trains at 10 and 100 Hz. Chronic stimulation of the denervated SOL resulted in twitch times-to-peak and half-relaxation times that varied in a graded manner between values longer than those in the normal SOL to values as fast as those in the normal EDL, depending upon the pattern used. Increasing pulse frequencies (constant number) resulted in faster twitches, lower twitch/tetanus ratios, increasing post-tetanic potentiations, and larger tetanic tensions. Increasing pulse numbers (constant frequencies) resulted in slower twitches, lower twitch/tetanus ratios, post-tetanic depressions, and higher fatigue indices. The effect of varying the pulse number on twitch parameters was greater at low frequencies (10-20 Hz) than at high frequencies (100 Hz). SOL muscles receiving pulse trains at both 10 and 100 Hz became much faster than muscles receiving pulse trains at 10 Hz only, even in the experiments where the stimulation pattern contained 9 times as many pulses at 10 as at 100 Hz. Chronic stimulation of both the denervated and the innervated EDL with large numbers of pulses at 10 or 15 Hz resulted in twitches that were only half as slow as those induced in the SOL by the same "slow" patterns. In addition, these patterns led to a marked decrease in maximum tetanic tension and a marked increase in twitch/tetanus ratio. During stimulation with a small number of pulses at 150 Hz, on the other hand, twitch speed, twitch/tetanus ratio, and maximum tetanic tension remained normal or almost normal. We conclude that the isometric twitch and related properties of the rat SOL muscle can be graded within wide "adaptive ranges" by varying either the number or the frequency of pulses. In the EDL, the corresponding adaptive ranges appear much narrower, suggesting that the EDL and the SOL contain intrinsically different muscle fibers.

Adaptation, Physiological↗

PubMed1987

Effects of chronic stimulation on the size and speed of long-term denervated and innervated rat fast and slow skeletal muscles.

This study seeks to identify the mechanisms which motoneurones use to control the contractile force and speed of skeletal muscles. We have stimulated directly slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles of adult rats intermittently at 100 Hz for 1-9 months. The muscles were either chronically denervated, denervated and reinnervated, or normally innervated. The stimulation started either immediately, or more commonly, after 1-9 months of denervation. Stimulation starting several months after denervation increased the mean maximum tetanic tension 37 times in SOL and eight times in EDL. These values represented 40 and 12% of the increases obtained by reinnervation after comparable periods of time. In denervated SOL and EDL muscles stimulated directly for more than 2 months, the mean isometric twitch contraction times were 13 and 12.7 ms, as in normal EDL muscles (13 ms). In innervated SOL muscles stimulated directly for 1-4 months, the mean twitch contraction times were 23.6 ms (normally innervated) and 19.2 ms (reinnervated), which were considerably shorter than in normal control SOL muscles (39.2 ms). Single motor unit recordings revealed that the natural (background) nerve impulse activity was essentially unaffected by the stimulation. Twitch contraction time and percentage of type II fibres in SOL muscles were related. The fastest muscles (denervated and stimulated) consisted of 100% type II fibres (with one exception), the second fastest (reinnervated and stimulated) of 70-50%, the third fastest (normally innervated and stimulated) of 45-0%, the second slowest (reinnervated) of 15-0%, and the slowest muscles (innervated controls) of 5-0% type II fibres.

Animals↗

PubMed1987

Gradation of force output in normal fast and slow muscles of the rat.

The discharge patterns of 16 motor units in extensor digitorum longus (EDL) and soleus (SOL) muscles of freely moving adult rats, described by Hennig & Lømo (1985), were further analysed with respect to their role in grading muscle force output. The units fell into three distinct classes, termed EDL-1, EDL-2 and SOL-1, probably corresponding to type FF, FR and S units. The EDL-1 units generated only single impulses or impulse trains of short duration (phasic firing) which had high frequency and usually started with a short interspike interval (initial doublet). The EDL-2 and SOL-1 units generated single impulses and impulse trains of both short and long durations (phasic and tonic firing) without initial doublets. The frequency was high in EDL-2 and low in SOL-1 units. In EDL-2 and SOL-1 units, the mean durations of the first interspike intervals in a train decreased as the number of impulses per train increased. In EDL-1 units they did not change. Both SOL and EDL muscles were simulated through the nerve at different regular frequencies and tension-frequency (T-F) curves constructed. The EDL-2 units fired naturally most often at frequencies corresponding to the steepest part of the EDL T-F curve. The EDL-1 and SOL-1 units fired naturally most often at frequencies where the T-F curves of their respective muscles began to flatten before maximum tetanic tension was reached. Stimulus trains starting with an initial doublet produced maximum rate of tension development (optimum impulse pattern). At optimum intervals the force increased from about 20 to 85% of maximum tetanic tension when the number of stimuli was increased from 1 to 7. It is concluded that the natural firing pattern of EDL-1 units and the contractile properties of EDL muscle fibres are normally matched so that the force can develop at maximum rate to maximum levels at the start of contractions. Tension output is apparently regulated primarily through varying number of impulses per train in EDL-1 units; in SOL-1 and EDL-2 units both rate and number of impulses are important.

Animals↗

PubMed1987

Control of end-plate channel properties by neurotrophic effects and by muscle activity in rat.

1. The formation of ectopic neuromuscular synapses was induced in rat soleus muscle by implantation of the fibular nerve into the proximal part of the muscle and subsequent sectioning of the soleus nerve. The gating properties of acetylcholine (ACh) receptors at the newly formed end-plates were examined by analysis of acetylcholine-induced membrane current fluctuations. 2. In agreement with earlier studies, the apparent mean open time of end-plate channels decreased during synaptic development from about 4 ms to about 1 ms (-60 mV membrane potential, 22 degrees C) within 7-18 days after the soleus nerve had been cut. 3. When the fibular nerve was cut at an early stage of end-plate development, fast-gating channels with apparent mean open times of 1 ms characteristic of mature end-plates did not develop within the next 10-14 days. 4. When the fibular nerve was cut at an early stage of end-plate development and the soleus muscle was then stimulated chronically via implanted electrodes, fast-gating channels did develop in the absence of the nerve terminals within 4-6 days. 5. When impulse conduction in the transplanted fibular nerve was blocked chronically at the time of soleus nerve section such that ectopic end-plates formed in inactive muscle, fast-gating channels developed within 12-14 days. 6. The results show that motoneurones control the conversion from slow-gating fetal to fast-gating adult-type ACh receptor channels at ectopic end-plates in rat soleus muscles. The conversion occurs in the absence of impulse activity provided the nerve continues to be present. However, it also occurs in the absence of the nerve provided the muscle is active and had received an early priming influence from the nerve. Thus, nerve-evoked muscle activity and nerve-released trophic influences complement each other in controlling the gating properties of junctional ACh receptor channels.

Action Potentials↗

PubMed1985

Motor endplates in fast and slow muscles of the rat: what determines their difference?

Motor endplates in fast and slow skeletal muscles have different functional and morphological characteristics, and for brevity, are termed fast and slow respectively. We have examined the terminal arborization patterns of fast fibular and slow soleus axons 3-4 and 6 months after they reinnervated old preformed endplates or formed new ectopic endplates with denervated rat soleus muscles. Ectopic endplates formed by transplanted fibular and soleus nerves were fast and slow in appearance respectively. Both the fibular and the soleus nerves formed endplates of slow appearance when they reinnervated the original endplates. The fast appearance of ectopic fibular nerve endplates was unaffected by reinnervation of the original endplates by the slow soleus nerve. Dually innervated fibres had intermediate contraction speed compared to the fast fibres reinnervated only by the fibular nerve and the slow fibres reinnervated only by the soleus nerve. Continuous stimulation of the transplanted fibular nerve at 10 Hz for 3-4 months, starting just before the onset of ectopic endplate formation, prevented the increase in contraction speed seen without stimulation. The ectopic endplates of the stimulated axons were much smaller than usual and showed some signs of fast to slow transformation, but the transformation was incomplete and varied in degree between preparations. Transplanted soleus axons were less prone to growing along foreign pathways and to forming ectopic endplates than fibular axons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Stimulation of denervated rat soleus muscle with fast and slow activity patterns induces different expression of acetylcholinesterase molecular forms.

The relative amount and distribution of acetylcholinesterase (AChE) molecular forms were studied in slow soleus and (less extensively) in fast extensor digitorum longus (EDL) muscles of the rat before and after denervation and direct stimulation. Normal EDL muscles showed higher total and specific AChE activity than normal soleus muscles and contained essentially three different molecular AChE forms (G1, G4, and A12) as opposed to six forms (G1, G2, G4, A4, A8, and A12) in the soleus. Denervation reduced AChE activity in both muscles. In the soleus direct stimulation starting 2 to 3 weeks after denervation increased the specific AChE activity markedly. The increase started 12 to 24 hr after the onset of stimulation, reached 3 to 5 times normal values after 2 to 7 days, and then declined gradually toward normal values over the next 2 weeks. Furthermore, the effect on the different molecular forms depended strongly on the stimulus pattern. Thus, intermittent 100 Hz stimulation (fast pattern) induced essentially the three forms typical of the normal EDL, whereas continuous 10 Hz stimulation induced the six forms characteristic of normal soleus muscles but with some differences in their relative proportions. In the EDL, 2 days of continuous 10 Hz stimulation (the only duration and pattern examined) failed to induce a similar increase in AChE activity.

Acetylcholinesterase↗

PubMed1984

Miniature end-plate potentials in rat skeletal muscle poisoned with botulinum toxin.

Spontaneous transmitter release, recorded as miniature end-plate potentials (m.e.p.p.s), was studied in rat extensor digitorum longus (e.d.l.) and soleus muscles partially or completely paralysed by botulinum toxin type A (BoTx). Normal unpoisoned muscles were examined for comparison. Analysis of m.e.p.p.s in both normal and BoTx-poisoned muscles confirmed the presence of two populations of potentials. One population, which comprised about 96% of the m.e.p.p.s recorded at non-poisoned end-plates, was characterized by a uniform time course and a mean time-to-peak of 0.5-0.7 ms. These potentials had a shape and time-to-peak similar to that of quantal end-plate potentials (e.p.p.s) evoked by nerve stimuli. These were designated 'fast m.e.p.p.s'. The other population of m.e.p.p.s was characterized by a slower, more variable rise-time, the time-to-peak exceeding 1.1 ms, and generally a larger amplitude. These were designated 'slow m.e.p.p.s'. In both partial and complete paralysis by BoTx the frequency of fast m.e.p.p.s was reduced by more than 90% and the reduction lasted several weeks. After 6-10 days of poisoning the frequency of slow m.e.p.p.s gradually increased. The highest frequency of slow m.e.p.p.s (0.4 Hz) was recorded in the partially paralysed soleus muscle, the frequency being about ten times that at unpoisoned end-plates. In both partially paralysed muscles slow m.e.p.p. frequency returned towards normal 28 days after poisoning. A significant correlation (r = 0.67) was observed between the quantal content of e.p.p.s and the frequency of fast m.e.p.p.s in partially paralysed e.d.l. muscles. No significant correlation was observed between quantal content of e.p.p.s and the frequency of slow m.e.p.p.s. To further study if muscle activity influenced the appearance of slow m.e.p.p.s, partially paralysed soleus muscles were directly stimulated in vivo during the first 11-13 days following BoTx poisoning, using a stimulation pattern which inhibits nerve terminal sprouting and the appearance of denervation changes. This procedure did not alter the frequency of slow m.e.p.p.s as compared to unstimulated poisoned controls. It is concluded that enhancement of slow m.e.p.p. frequency in muscles poisoned with BoTx is related to the blockade of evoked Ca2+-dependent quantal transmitter release. However, additional factors influence this type of spontaneous and Ca2+-insensitive release of acetylcholine since there is a great variability between fibres and a time lag between the disappearance of fast m.e.p.p.s and the activation of slow m.e.p.p. frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗