503 research outputs found

    Calcitonin gene-related peptide: possible role in formation and maintenance of neuromuscular junctions

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    The expression and content of calcitonin gene-related peptide (CGRP) and secretogranin II (SgII) in adult rat motor neurons were examined by in situ hybridization, Northern blot analysis, and immunocytochemistry. Normal motor nerve terminals did not contain detectable CGRP or SgII. Ten to 15 days after a peripheral nerve crush about 80% of the motor nerve terminals reinnervating the soleus (SOL) muscle contained detectable CGRP but no SgII. Thereafter, the percentage of CGRP-positive terminals declined towards zero. In the spinal cord, CGRP expression was higher than normal 1 d after a sciatic nerve crush and increased during the next few days. No increase in SgII expression was observed. Nerve blocks by tetrodotoxin (TTX) and botulinum toxin (BoTX) increased CGRP content and expression in motor neurons but had no effect on SgII. After 10 d of BoTX treatment and 33 d of TTX treatment (the longest time points studied), more than 90% of the motor nerve terminals stained for CGRP. The density of large dense core vesicles (LDCVs) was also higher than normal in such terminals. Some increase in CGRP content and expression occurred in the nontreated side. In a group of rats, the peroneal nerve was stimulated electrically with brief, intermittent pulse trains at 100 Hz. The stimulation was applied below a TTX block that had started 7 or 19 d earlier. One minute of such stimulation was sufficient to remove CGRP from most of the terminals.(ABSTRACT TRUNCATED AT 250 WORDS

    Regulation of turnover and number of acetylcholine receptors at neuromuscular junctions

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    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

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

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    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

    Effects of chronic nerve conduction block on formation of neuromuscular junctions and junctional AChE in the rat

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    The 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.

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    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

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

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    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

    Viskositetsmodellering av basaltiska lavor, exempel från Lomo Negro, El Hierro, Tajogaite, La Palma och Fagradalsfjall, Island

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    Magma viscosities are essential for understanding the hazard of volcanic eruptions. Depending on viscosity parameters, lavas can move quickly or with great resistance. This study examines how chemical composition, volatiles and crystals affect the viscosity of Lomo Negro, a mafic flow on El Hierro with a proportion of crystals visible to the naked eye. Geochemical compositions from the site along with data from two other lava flows for comparison, the 2021 Tajogaite eruption on La Palma and the 2021 Fagradalsfjall eruption on Iceland, were used to calculate the dry melt viscosities. Lomo Negro had the lowest dry melt viscosity of the three locations, which is concluded to be linked to the low silica content, and high MgO and FeO(T) content. With complementary data, viscosity with volatiles was calculated. The results show how volatiles significantly decrease magma viscosity. Crystals increase magma viscosity, and the largest increase was calculated for Lomo Negro. Despite this, the samples from Lomo Negro exhibit lower viscosities than the majority of the measured samples. This is concluded to be due to the geochemistry of the samples, and highlights how the lava has been able to flow despite its large crystal content.Magmaviskositet är avgörande för att förstå hur farligt ett vulkanutbrott kan bli. Viskositetsparametrar kan avgöra om ett flöde får en hög eller låg hastighet. Denna studie undersöker hur geokemisk sammansättning, volatiler och kristaller påverkar viskositeten hos Lomo Negro, ett mafiskt flöde på El Hierro med en hög andel kristaller som är synliga för blotta ögat. Geokemisk data från Lomo Negro användes tillsammans med data från två andra lavaflöden, Tajogaite-utbrottet på La Palma 2021 och Fagradalsfjall-utbrottet på Island 2021, för att beräkna och jämföra viskositeter utan volatiler. Lomo Negro hade den lägsta viskositeten av de tre platserna, vilket konstateras vara kopplat till flödets låga SiO2-halt och höga MgO- och FeO(T)-halt. Med kompletterande volatildata beräknades viskositeten med volatiler, och resultaten visar hur volatiler minskar magmaviskositeten signifikant. Kristaller ökar magmaviskositeten och den största ökningen beräknades för Lomo Negro. Trots detta uppvisar proverna från Lomo Negro lägre viskositeter än majoriteten av övriga prover. Detta antas bero på provernas geokemi, och belyser hur lavan har kunnat flöda trots sitt höga kristallinnehåll

    Viskositetsmodellering av basaltiska lavor, exempel från Lomo Negro, El Hierro, Tajogaite, La Palma och Fagradalsfjall, Island

    No full text
    Magma viscosities are essential for understanding the hazard of volcanic eruptions. Depending on viscosity parameters, lavas can move quickly or with great resistance. This study examines how chemical composition, volatiles and crystals affect the viscosity of Lomo Negro, a mafic flow on El Hierro with a proportion of crystals visible to the naked eye. Geochemical compositions from the site along with data from two other lava flows for comparison, the 2021 Tajogaite eruption on La Palma and the 2021 Fagradalsfjall eruption on Iceland, were used to calculate the dry melt viscosities. Lomo Negro had the lowest dry melt viscosity of the three locations, which is concluded to be linked to the low silica content, and high MgO and FeO(T) content. With complementary data, viscosity with volatiles was calculated. The results show how volatiles significantly decrease magma viscosity. Crystals increase magma viscosity, and the largest increase was calculated for Lomo Negro. Despite this, the samples from Lomo Negro exhibit lower viscosities than the majority of the measured samples. This is concluded to be due to the geochemistry of the samples, and highlights how the lava has been able to flow despite its large crystal content.Magmaviskositet är avgörande för att förstå hur farligt ett vulkanutbrott kan bli. Viskositetsparametrar kan avgöra om ett flöde får en hög eller låg hastighet. Denna studie undersöker hur geokemisk sammansättning, volatiler och kristaller påverkar viskositeten hos Lomo Negro, ett mafiskt flöde på El Hierro med en hög andel kristaller som är synliga för blotta ögat. Geokemisk data från Lomo Negro användes tillsammans med data från två andra lavaflöden, Tajogaite-utbrottet på La Palma 2021 och Fagradalsfjall-utbrottet på Island 2021, för att beräkna och jämföra viskositeter utan volatiler. Lomo Negro hade den lägsta viskositeten av de tre platserna, vilket konstateras vara kopplat till flödets låga SiO2-halt och höga MgO- och FeO(T)-halt. Med kompletterande volatildata beräknades viskositeten med volatiler, och resultaten visar hur volatiler minskar magmaviskositeten signifikant. Kristaller ökar magmaviskositeten och den största ökningen beräknades för Lomo Negro. Trots detta uppvisar proverna från Lomo Negro lägre viskositeter än majoriteten av övriga prover. Detta antas bero på provernas geokemi, och belyser hur lavan har kunnat flöda trots sitt höga kristallinnehåll
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