Electron microscopic study of extraocular muscles in myotonic dystrophy

A study was made of the effect of morphine on electrical activity within single ganglia of Auerbach's plexus of guinea pig longitudinal muscle-myenteric plexus as monitored by means of external electrodes. Morphine produces a concentration dependent block of single spike activity. This effect is competitively antagonized by naloxone. The ED50 for morphine effect is about 7 X 10(-7) M. Naloxone and dextrorphan have no effect on electrical activity. Acetylcholine in the concentration range of 10(-7)--10(-5) M augments electrical activity of ganglia. Morphine has little if any effect on the enhanced stimulation produced by acetylcholine thus indicating that the drug does not act directly upon the ganglion. Our results suggest that a specific opiate receptor is present on the preganglionic nerve terminals and that morphine and other opiates block ganglionic transmission by inhibiting the release of preganglionic acetylcholine.     

Sensory terminals on extrafusal muscle fibres in myotendinous regions of developing rat muscles

Axon terminals were observed to form neuromuscular contacts with extrafusal muscle fibres in myotendinous regions of developing rat muscles up to 5 days after birth. These neuromuscular contacts are found in fascicles of muscle fibres connected with differentiating Golgi tendon organs. Axon terminals establishing these contacts are obviously sensory, since they do not degenerate after de-efferentation performed in neonatal rats. The terminals contain mainly clear and dense core vesicles and form neuromuscular connections resembling developing motor endplates, with a cleft about 60 nm wide and basal lamina interposed between the axolemma and the sarcolemma. Each terminal, however, also forms a close contact in a restricted region where the basal lamina is missing; there the cleft is reduced to 20 nm and the axolemmal and sarcolemmal membranes are linked by desmosome-like attachment plaques. After the fifth postnatal day, axon terminals become detached from muscle fibres and are only found among collagen bundles of the tendon organ. The functional significance of these temporary neuromuscular contacts is not clear.     

Activation of two types of brain glutamate dehydrogenase isoproteins by gabapentin

In the present investigation, the benefit of physical training in patients with inflammatory myopathy was studied. In this prospective, randomized, controlled study, 14 patients with polymyositis (PM) or dermatomyositis (DM) were investigated. The training, consisting of bicycle exercise and step aerobics, took place over a 6 week period. Baseline and endpoint measurements included an 'activities of daily living' (ADL) score, peak isometric torque (PIT) generated by muscle groups in the lower extremities, peak oxygen consumption (VO2max), and creatine phosphokinase (CPK) levels. There was no significant rise in disease activity in the training group in comparison to the controls. The ADL score for the treatment group, in comparison to the control group, improved (P < 0.02), PIT rose (P < 0.05) and there was a statistically significant increase in oxygen uptake relative to body weight (P < 0.05). No rise in inflammatory activity, but significant improvement in muscle strength, oxygen uptake and well-being, were found in patients with inflammatory myopathy as a result of physical training. Besides medication, a physical training programme consisting mainly of concentric muscle contractions should therefore be an integral part of therapy, particularly in view of the cardiopulmonary risk of these patients.     

Near-resonance saturation pulse imaging of the extraocular muscles in thyroid-related ophthalmopathy

PURPOSE: We examined the utility of near-resonance saturation pulse imaging (magnetization transfer [MT] and spin lock) in characterizing microstructural changes occurring in the extraocular muscles of patients with thyroid-related ophthalmopathy (TRO). METHODS: Eight healthy volunteers and 10 patients with TRO were imaged using an off-resonance saturation pulse in conjunction with conventional spin-echo T1-weighted imaging at frequency offsets of 500, 1000, 1500, and 2000 Hz from water resonance. The relative contributions of MT and spin-lock excitation to image contrast at each frequency offset were estimated using a computer simulation model. Suppression ratios were calculated for the control and TRO groups from measurements obtained on two successive coronal sections in the widest portion of the inferior and medial rectus muscles bilaterally. A repeated measures analysis of variance and a parametric correlation analysis were performed to evaluate maximum cross-sectional area, MR-generated signal, and suppression ratios for the extraocular muscles examined. RESULTS: Our computer model suggested that saturation of extraocular muscles was due to pure MT effects with our off-resonance pulse at 2000 and 1500 Hz, to a combination of MT and spin lock at 1000 Hz frequency offset, and, primarily, to spin-lock excitation at 500 Hz frequency offset. Suppression ratios for the extraocular muscles of the TRO patients were significantly lower than that observed for the control subjects at 1500, 1000, and 500 Hz frequency offset. This differential saturation effect was maximal at 500 Hz frequency offset, with mean suppression ratios for the inferior and medial rectus muscles of 27% for the healthy subjects and 20% for the TRO group. CONCLUSION: Both MT and spin-lock contrast of the extraocular muscles in patients with TRO differ significantly from that observed in control subjects. Near-resonance saturation pulse imaging may enhance our understanding of the microstructural changes occurring in the extraocular muscles of these patients.     

Signals of eye position and velocity in the first-order afferents from pigeon extraocular muscles

Responses of first-order afferents from the extraocular muscles of the pigeon were studied by extracellular recording in the ophthalmic part of the trigeminal ganglion of decerebrate, paralysed pigeons. The afferents responded to both the amplitude and velocity of ramp displacements of the intact eye with amplitude sensitivities ranging from 0.9 to 8 impulses/s/deg of eye displacement beyond the response threshold. Once a new stable position had been reached, the afferent signal depended only upon the absolute position of the eye within the orbit. The responses adapted in seconds rather than minutes so these units would not provide a continuous signal of the position of an immobile eye; they are best described as signalling position and velocity in relation to eye movements.     

Acute paresis of extraocular muscles associated with IgG anti-GQ1b antibody

There have been several case reports of acute ophthalmoparesis without ataxia subsequent to infection or immunization. The nosological position and therapy for acute ophthalmoparesis have yet to be established. Sera from patients are reported to have IgG anti-GQ1b antibody, which is frequently found in sera from patients with Fisher's syndrome. To establish the etiology of acute ophthalmoparesis, I tested sera from 8 patients with acute ophthalmoparesis for anti-GQ1b antibody. High IgG anti-GQ1b antibody titers were present in sera from patients in the acute phase of the illness. I describe the successful treatment with plasmapheresis and intravenous immunoglobulin. Some cases of acute ophthalmoparesis following infection or immunization may be categorized as an auto-immune disease related to Fisher's syndrome.     

Features of myoneural junctions in the extraocular muscles of the opossum (Didelphis albiventris)

The myoneural junctions present in the opossum (Didelphis albiventris) extraocular muscles were studied through histochemical and ultrastructural techniques. Three different types of junction were shown: two single types, 'en grappe' and 'en plaque', present in the middle third of the muscle fibers; and one multiple type, more rare and observed in the distal third of the muscle.     

Afferent signals from the extraocular muscles of the pigeon modify the vestibulo-ocular reflex

Although the extraocular muscles (EOM) contain stretch receptors it is generally thought that the afferent signals which they provide play no role in the control of eye movement. We have previously shown that these afferent signals do modify both the vestibular responses of single units in the oculomotor control system and the electromyographic responses of the EOM during the vestibulo-ocular reflex (VOR). We have now investigated the effect of EOM afferent signals on the VOR itself, by recording the electro-oculogram of one eye while imposing movements on the other eye during the VOR. Moving the eye in a manner which mimics the slow phase of the VOR, we have found that, as the peak velocity of the imposed eye movement increases, the amplitude of eye movement of the other eye decreases. These results confirm that the output of the VOR itself, expressed as movement of the globe, and not merely some of its component parts, is modified by EOM afferent signals.     

Localization of motoneurons innervating the extraocular muscles of the sheep by retrograde fluorescent tracers

Retrograde transport of the fluorescent tracers Fast blue, Evans blue, Diamidino yellow dihydrochloride, and Propidium iodide was used to determine the location of the motoneurons innervating the extraocular muscles of the sheep. An extensive superposition among the motor pools of the oculomotor nucleus (ON) has been observed. In the rostral third of the ON, a considerable merging occurs between obliquus ventralis and rectus medialis motoneurons and also between rectus ventralis and rectus medialis motoneurons. In the middle third of the ON, rectus dorsalis and levator palpebrae superioris motoneurons are intermingled with each other, and also with obliquus ventralis motoneurons dorsally and with rectus medialis motoneurons ventrally. The rostral portion of the trochlear nucleus overlaps with the caudal pole of the ON. The motoneurons innervating the obliquus dorsalis muscle are mainly contralateral with few ipsilateral exceptions. The retractor bulbi muscle receive the innervation by both the abducens and accessory abducens nuclei.     

Lateral rectus whole muscle and motor unit contractile measures with the extraocular muscles intact

Both extracellular and intracellular stimulation of single motoneurons were shown to be similarly effective and consistent in eliciting contractile responses in single lateral rectus muscle motor units. The whole muscle was activated by stimulating the sixth nerve in the brain stem. Both whole muscle and motor unit contractile characteristics, under isometric conditions, were found to remain consistent regardless of whether this extraocular muscle was detached or left attached to the globe. In addition, whole muscle twitch and maximum tetanic tension evoked by sixth nerve stimulation was significantly less than would be predicted by the linear summation of individual motor unit twitch and maximum tetanic tensions.     

Differential effects of a six-day immobilization on newborn rat soleus muscles at two developmental stages

Our objective was to determine the effects of a six-day immobilization on the musculoskeletal system of the rat during postnatal development at two key periods when the states of innervation are known to be different. This work was undertaken on the soleus muscle since it is well known that postural slow muscles show marked changes after a period of disuse. Thus, the soleus muscle was immobilized in a shortened position either when the innervation was polyneuronal or monosynaptic, respectively from 6 to 12 and from 17 to 23 days. The muscle modifications were followed by ATPase staining and myosin heavy chain (MyHC) isoform identification using monoclonal antibodies and SDS-PAGE. The functional properties of skinned fibre bundles were established by calcium/strontium (Ca/Sr) activation characteristics. In control muscles the maturation was characterized by a progressive increase of adult MyHCs (I and IIA) concomitant with a decrease in both the MyHC neo and the Ca affinity. Between 6 to 12 days, immobilization of the limb induced an increase in histochemical type IIC fibres. Using antibodies we identified new fibre types, classified as a function of their MyHC isoform co-expression. We observed an increase in expression of both MyHC neo and Ca affinity. From 17 to 23 days, the immobilization induced an increase in Ca affinity and marked changes in the MyHC isoform composition: disappearance of MyHC neo and expression of the fast MyHC IIB isoform, which in normal conditions is never expressed in the soleus muscle. We conclude that an immobilization imposed during polyneuronal innervation delays the postnatal maturation of the soleus muscle, whereas when the immobilization is performed under monosynaptic innervation the muscle evolves towards a fast phenotype using a default pathway for MyHC expression.     

Comparison of glycine- and GABA-evoked currents in two types of neurons isolated from the rat striatum

Strychnine-sensitive glycine-activated currents and gamma-aminobutyric acid (GABA)-activated currents were compared in two types of neurons acutely isolated from striatal slices by vibrodissociation: large cells, presumably cholinergic giant aspiny neurons (GAN) and medium sized cells, presumed medium spiny neurons (MSN). Whole cell voltage clamp and concentration jump techniques were used. All cells responded to glycine (10-1000 microM) and GABA (2-100 microM), in MSN and GAN the maximal responses to glycine were 50 and 120% of the GABA response, respectively. GABA- and glycine- responses were additive and blocked selectively by bicuculline (1 microM) and strychnine (50 nM), respectively. These results predict the presence of alpha- and beta-subunits of the glycine receptor in the striatum.     

Combined paresis and restriction of the extraocular muscles after orbital fracture: a study of 16 patients

Sixteen patients with combined paresis and restriction of extraocular muscle(s) orbital fracture repair were studied before and after in order to determine the clinical features and management of such patients. All 16 patients showed limited ductions of the involved eye in the field of action of the entrapped, paretic muscle and of the antagonist muscle after orbital fracture. Single extraocular muscles (13 patients) and two extraocular muscles (three patients) were demonstrated adjacent to the fracture site on orbital computed tomography (CT). In three patients prior to orbital surgery, a deviation in primary position was present. After fracture repair with release of the entrapped muscle in all patients, evidence of paresis of the muscle was demonstrated by underaction in its field of action and overaction in the field of its antagonist. There was a resultant manifest tropia or phoria in the primary position. In seven patients, the paresis gradually improved with no tropia and little diplopia in the functional fields of gaze. Three patients had minimal deviations and required no further treatment. Six patients with significant deviations required prisms (three patients) or strabismus surgery (three patients). The latter three patients had two muscles involved. Results of this study demonstrate that the ophthalmologist must appropriately diagnose patients with paresis and restriction of an extraocular muscle and counsel them that "new" diplopia may occur after orbital fracture repair and that this diplopia may require additional therapy.     

Activation of two types of Ca2+-permeable nonselective cation channel by endothelin-1 in A7r5 cells

1. In A7r5 cells loaded with the Ca2+ indicator fura-2, we examined the effect of a Ca2+ channel blocker SK&F 96365 on increases in intracellular free Ca2+ concentrations ([Ca2+]i) and Mn2+ quenching of fura-2 fluorescence by endothelin-1 (ET-1). Whole-cell patch-clamp was also performed. 2. Higher concentrations (> or = 10 nM) of ET-1 (higher [ET-1]) evoked a transient peak and a subsequent sustained elevation in [Ca2+]i: removal of extracellular Ca2+ abolished only the latter. A blocker of L-type voltage-operated Ca2+ channel (VOC) nifedipine at 1 microM reduced the sustained phase to about 50%, which was partially sensitive to SK&F 96365 (30 microM). 3. Lower [ET-1] (< or = 1 nM) evoked only a sustained elevation in [Ca2+]i which depends on extracellular Ca2+. The elevation was partly sensitive to nifedipine but not SK&F 96365. 4. In the presence of 1 microM nifedipine, higher [ET-1] increased the rate of Mn2+ quenching but lower [ET-1] had little effect. 5. In whole-cell recordings, both lower and higher [ET-1] induced inward currents at a holding potential of -60 mV with linear I-V relationships and reversal potentials close to 0 mV. The current at lower [ET-1] was resistant to SK&F 96365 but was abolished by replacement of Ca2+ in the bath solution with Mn2+. The current at higher [ET-1] was abolished by the replacement plus SK&F 96365. 6. In a bath solution containing only Ca2+ as a movable cation, ET-1 evoked currents: the current at lower [ET-1] was sensitive to Mn2+, whereas that at higher [ET-1] was partly sensitive to SK&F 96365. 7. These results indicate that in addition to VOC, ET-1 activates two types of Ca2+-permeable nonselective cation channel depending on its concentrations which differ in terms of sensitivity to SK&F 96365 and permeability to Mn2+.     

Early cerebellar hemispherectomy in the rat. Effects on the maturation of two hindlimb muscles and on lumbar motoneurones

Cerebellar hemispherectomy before the 10th day in rats leads to extensive neuronal remodelling. In the present study the problem was studied whether such early lesions also have effects on the maturation of the soleus and the extensor digitorum longus muscles in the hindleg as well as on the formation of dendrite bundles from motoneurons innervating the soleus muscle. Results indicate consistent left-to-right differences in the numbers of muscle fibres but no differences in muscle differentiation. Dendritic bundles of soleus motoneurons, at the side ipsilateral to the cerebellar lesion are absent or less conspicuous in comparison to the contralateral side or to those bundles in normal rats. Cerebellar lesioning at the 30th day does not affect dendritic bundles.     

Expression of extraocular-superfast-myosin heavy chain in rat laryngeal muscles

Superfast myosin heavy chain (MHC), which is found in jaw-closing muscle and extraocular muscle (EOM), may also be found in rat laryngeal muscles. Immunostaining and Western blot using anti-EOM antibody were performed to identify and localize EOM MHC in laryngeal muscles. Specific reactivity of laryngeal IIL MHC was confirmed by Western blot and on immunostaining, all fibers in the lateral part of thyroarytenoid muscle reacted with EOM antibody. A scattered pattern of positive fibers was observed in the medial part of the thyroarytenoid, the posterior cricoarytenoid and the lateral cricoarytenoid muscles. EOM MHC was not detected in the cricothyroid muscle. The expression of EOM MHC in rat laryngeal muscle is consistent with the functional demands of the airway protection reflex.