Post-contraction changes in human muscle spindle resting discharge and stretch sensitivity

Summary The activities of human muscle spindle primary endings were recorded in the lateral peroneal nerve using the microneurographic method. The aim of the study was to test whether voluntary isometric contraction causes any after-effects, first in the resting discharge of muscle spindle primary endings and secondly in their responses to a slow ramp stretch. To investigate the latter point, the initial angular position of the ankle was passively adjusted until the unit fell silent, in order to introduce a delay in the responses to muscle stretch. The results were as follows: (1) most of the units did not exhibit the post-contraction sensory discharge reported to occur in numerous animal experiments; this means that the muscle spindle resting discharge was essentially the same before and after isometric voluntary contraction. (2) Isometric voluntary contraction led to changes in muscle spindle stretch sensitivity which resulted in a reduction in the stretch threshold and a decrease in the muscle spindle dynamic sensitivity. These data suggest that the after-effects observed may have been triggered by static fusimotor neurones. The results are discussed with reference to the theory according to which the processing by the CNS of muscular proprioceptive messages deals mainly with signals arising from muscles stretched during movement, and it is concluded that the coactivation of and y motoneurones during the contraction facilitates the coding of the parameters of forthcoming stretching movements, by the muscle spindles.     

The effects on primary and secondary spindle afferents of fusimotor reflex during ramp and sinusoidal muscle stretch

Summary Tetanic stimulation of ipsilateral Triceps surae afferents leads to a reflex increase in the initial burst from the primary spindle afferents during ramp stretch in both intercollicular decerebrate and spinal preparations. The dynamic index does not change significantly.Slow, low-amplitude sinusoidal muscle stretches (1.6 Hz, 0.55 mm peak-peak) disclose an increased dynamic sensitivity of primary afferents during reflex activation. The same activation in the statically adapted muscle results in a great many cases in little or no increase in spindle discharge rate.In the frequency-stretch relation, the discharge rates of primary afferents in the spinal cat and of secondaries in decerebrate animals are greatly increased by combined fusimotor activation and low-amplitude sinusoidal stretch.We conclude that both static and dynamic motoneurons are implied in this reflex.     

A displacement servosystem for muscle research permitting 50 μm length changes within 40 μs

In order to determine the tension response of a stimulated intact muscle fibre to a very fast length change a servo system has been developed capable of imposing a displacement of 50 m i.e. about 1% of the fibre length, within 40 s. The system is designed so as to limit the displacement overshoot to less then 1%. This paper presents the performance of the system; both unloaded and loaded with a muscle fibre.     

Effect of endurance exercise on fibre type composition and muscle weight of reinnervating rat plantaris muscle

The purpose of this study was to evaluate the effect of endurance exercise on the histochemistry and wet weight of the reinnervating rat plantaris muscle. Two groups of young female Wistar rats (6 weeks old), 1 sedentary denervated control (n=13) and 1 excercised denervated experimental (n=17), were denervated unilaterally by cutting and resecting the sciatic nerve. To effect reinnervation a skin grafting operation was carried out on the nerve so that the gap caused by resection was bridged. The third group was the sedentary non-denervated normal control (n=10). A progressive training program of 18 weeks of treadmill running was carried out by the experimental group. Approximately 5 months after denervation, the plantaris muscles were studied histochemically for reduced nicotinamide adenine dinucleotide diaphorase (NADH-D) and mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) activities. Fibres were classified as red, white, or intermediate with NADH-D. Alpha-GPD differentiates intermediate from red fibre types in case of difficulty in differentiating these fibre types from each other with NADH-D. The weight of the reinnervated plantaris muscle increased significantly after exercise. The exerise did not change the fibre type proportions — including red fibre type — in the deep region of the reinnervating plantaris. There were significant differences between normal control and denervated control or experimental groups in histochemical fibre populations in the deep region of the plantaris. The findings of this study suggest that: (a) treadmill running did not increase the oxidative capacity of the deep region of the reinnervating rat plantaris muscle; (b) treadmill training did not damage the reinnervating plantaris; (c) the presence of type grouping following reinnervation was not affected by training (exercise did not interfere with reinnervation).     

Sprouting of fusimotor neurones after partial denervation of the cat soleus muscle

Summary Normally, motoneurones innervate only the intrafusal fibres of muscle spindles. This is a report of sprouting of motoneurones to innervate extrafusal muscle fibres following partial denervation of the soleus muscle of kittens. In eight newborn animals, the L7 ventral root was cut on one side under anaesthesia and the animals were then allowed to recover. At approximately 100 days of age animals were reanaesthetised and a study made of mechanical properties of motor units whose axons ran in the S1 ventral root and supplied the partially denervated soleus muscle. Evidence was obtained for sprouting of all surviving motoneurones. In addition, in four experiments axons conducting within the range, on stimulation, produced measurable tension. In one experiment, stimulation of one such axon also produced specific fusimotor effects on four afferents identified as coming from primary endings of muscle spindles. The axon was therefore a fusimotor axon. The effect observed on stimulation of the axon suggested a largely dynamic action. Other examples of axons were encountered that on stimulation produced tension, but which could not be specifically associated with spindles. In addition, a number of axons that did not develop tension were shown, on stimulation, to have fusimotor effects that were static in action. It is concluded that in extensively denervated muscles motoneurones may sometimes sprout to innervate extrafusal fibres. The mechanical properties of the extrafusal fibres innervated by such axons were similar to those of ordinary motor units.     

Tension development and calcium sensitivity in skinned muscle fibres of the frog

Calcium activated isometric tension development was measured in single skinned muscle fibres of the ileofibularis muscle of the frog. The experiments were carried out at 5°C, pH=6.9, 1 mM free Mg²⁺ and an ionic strength of 160 mM. A Hill curve was fitted to the isometrically developed tension at different Ca²⁺ concentrations by means of a non-linear least mean square approximation. At a sarcomere length of 2.15 m, the Ca²⁺ concentration for half maximum tension (K) was 1.6 M. This Ca²⁺ concentration decreased with increasing sarcomere length; at 2.7 m, K was 1.1 M and at 3.1 m, K was 0.9 M. Therefore, Ca sensitivity is increased at larger sarcomere lengths. Consequently, the optimal sarcomere length for tension development shifted to larger values when the Ca²⁺ concentration was lowered. Osmotic compression of the fibre at 2.15 m by means of 5% Dextran also caused an increase in Ca sensitivity (K was 1.0 M). At 2.7 m, addition of 5% Dextran hardly affected the Ca sensitivity. The possible role of the interfilament spacing in the explanation of these results discussed.     

Quantitative and histochemical aspects of the differentiation of muscle spindles in the anterior latissimus dorsi of the developing chick

Summary The differentiation of muscle spindles has been investigated both quantitatively and histochemically in the slow anterior latissimus dorsi (ALD) muscle during embryonic and post-hatching development of the chick. The first spindles are detected by the 13th day in ovo, and a rapid increase in number takes place until the 15th of embryonic life. Two histochemical fibre types of intrafusal fibres are distinguished as early as the 13th day of embryonic development when myofibrillar ATPase activity is demonstrated after acid preincubation. In ALD muscle from post-hatched animals, two intrafusal fibre types are also distinguished by histochemistry: one fibre type is characterized by an acid and alkali-stable myofibrillar ATPase activity while this activity is acid-labile and alkali-stable in the other type. As far as the properties of myofibrillar ATPase are concerned, such types of intrafusal fibres resemble the extrafusal and fibre types defined recently in ALD muscle.The development of spindles in the slow-tonic ALD muscle is compared to the differentiation of spindles in the fast-twitch posterior latissimus dorsi (PLD) muscle of the chick which has been previously described (Toutant et al. 1981).     

Tityusγ toxin,a high affinity effector of the Na+ channel in muscle,with a selectivity for channels in the surface membrane

Toxin from the venom ofTityus serrulatus scorpion produces a partial block of the surface Na⁺ channel in frog muscle. This block occurs with no change in the voltage-dependence or in the kinetics of the remaining surface Na⁺ current. The partial blockade of Na⁺ channel activity occurs with no change in tubular Na⁺ currents nor in twitch tension. The maximum effect of the toxin is attained at concentrations as low as 3×10^–10 M. Hyperpolarization to potentials more negative than the resting potential (E=–90 mV) reduces or abolishes the effect of the toxin.Radioiodinated toxin binds to frog muscle membranes with a very high affinity corresponding to a dissociation constant of about 1×10^–11 M. Data obtained with both rabbit and frog muscle indicate that toxin is specific for Na⁺ channels in surface membranes. Toxin does not seem to bind to Na⁺ channels in T-tubule membranes. The biochemical data are in good agreement with electrophysiological studies and data on contraction. There is oneTityus toxin binding site per tetrodotoxin binding site in surface membranes. Competition experiments have confirmed thatTityus toxin binds to a new toxin receptor site on the Na⁺ channel structure. This site is the same that the toxin II fromCentruroides suffusus binding site, but this toxin has 100 times less affinity for the Na⁺ channel thanTityus toxin.     

Action of single dynamic fusimotor neurones on cat soleus Ia afferents during muscle shortening

Summary 1. The ability of single dynamic fusimotor (d) fibres to sustain the firing of muscle spindle primary (Ia) afferents during shortening was investigated in soleus muscles of anaesthetised cats. 2. Of 11 d fibres, 10 could maintain Ia firing during 10 mm/s shortening. Of the 7 tested at greater velocities, 5 could maintain Ia firing during shortening at velocities greater than 50 mm/s. 3. This ability was, however, critically dependent upon the timing of the stimulation. In particular, it rapidly reduced with increasing duration of stimulation before the onset of shortening. Furthermore, if appreciable stretch occurred between the onset of _d stimulation and the onset of shortening, this could greatly reduce the ability of _d fibres to sustain Ia discharge. 4. If _d neurones are on occasion phasically activated during voluntary shortening movements, their action could be an important determinant of Ia firing, even in the presence of weak _s action. Therefore in chronic recordings, observation of Ia firing during muscle shortening is not an adequate criterion for inferring _d activity.     

Some observations on responses evoked by pinna stimulation in efferent and afferent fibres innervating hind limb muscle spindles of the rat

Summary Pinna stimulation has long been known to evoke reflex changes of discharge in efferents to the hind limb and hence changes in muscle spindle discharges. The present experiments were made in the rat to determine the involvement of the static and dynamic fusimotor systems in the pinna reflex.We first observed fusimotor activity indirectly, by recording spindle responses to various length changes with and without concurrent pinna stimulation. Afferent responses were clearly influenced by static fusimotion during the reflex; evidence for dynamic fusimotion was sought but not found. Ipsilateral and contralateral stimuli appeared equally effective in evoking this static fusimotion.The magnitudes of afferent responses differed markedly between muscles. Observations were made simultaneously on activities recorded directly from efferents to peroneal and soleus muscles. Several efferents were spontaneously active in each nerve; pinna stimulation usually enhanced their activities and aroused also several others, previously quiescent. The frequencies of discharge in efferents to peroneus were usually higher than in those to soleus. This must in part be responsible for differences in afferent responses. The spontaneously active and activated fibres together formed about one quarter to one third of the total motoneurone pool and had conduction velocities restricted to the lower end of the conduction velocity spectrum for fibres.     

Neural and Mechanical Contributions to the Stretch Reflex: A Model Synthesis

A model for the soleus stretch reflex in the decerebrate cat was synthesized from models of the neural and muscular components, including the two proprioceptors (the muscle spindle and Golgi tendon organ) and their associated afferents (Ia, II, and Ib), the motoneuron pool with its reflex pathways, the branches of the motoneurons to the intrafusal muscles ( innervation), and the extrafusal muscle. Parameters for the muscle and receptor models were chosen independently to match their responses in isolation. Reflex gains and inputs were estimated to fit the response to stretch measured by Nichols and Houk. The chosen reflex gains and inputs are not unique; many different combinations reproduced the characteristic stretch response. With a single set of fixed parameters, the model predicted many mechanical properties of the stretch reflex, including linearization effects (when the stretch magnitude and direction are varied), as well as the dependence on operating force and initial muscle length. The model did not accurately predict the responses at higher stretch velocities, due to failure of the extrafusal muscle model. © 2002 Biomedical Engineering Society. PAC02: 8719Ff, 8719Rr, 8719La     

Inhibition of extensorγ motoneurons by antagonistic primary and secondary spindle afferents

Summary About 2/3 of the efferents isolated from the medial gastrocnemius nerve were inhibited by longitudinal high-frequency vibration applied to the tendons of the non-contracting pretibial flexors (decerebrate cats). The inhibition appeared at 15–25 m amplitude of vibration and increased up to a maximum at nearly 100 m. Increasing the frequency of vibration from 100 to 300 Hz increased the inhibition. The reflex effects elicited by muscle vibration corresponded well in incidence and magnitude with those evoked by tetanization of the deep peroneal nerve at group I stimulus strength. The reflex disappeared when the nerve supply of the vibrated muscles was cut. The sensitivity of some pretibial proprioceptors to vibration was also tested. It is concluded that primary spindle endings of the pretibial flexors inhibit the extensor motoneurons. Some findings hint at a spinal pathway involving I a inhibitory interneurons.In addition, an inhibitory action of pretibial group II afferents, probably secondary spindle endings, on extensor efferents was demonstrated.The described fusimotor inhibition by antagonistic muscle spindle afferents is a further example of --linkage.     

On muscle strength and the threshold of anaerobic work

Summary 1.When subjects are exercised on a bicycle ergometer at 80% of aerobic power, there is a progressive increase of arterial lactate for 5–15 min, and in subjects of poor cardio-respiratory fitness the terminal level may approach that found in maximal exercise. 2. 5 min of sub-maximal exercise at 70 or 80% of aerobic power leads to a substantial accumulation of arterial lactate (38.3±8.9, 47.6±8.9 mg/100 ml) respectively. 3. The arterial lactate levels following 5 min of sub-maximal exercise are negatively correlated with the strength of hand-grip and knee extension. 4. Evidence is presented that lactate accumulation represents an effect of muscle contraction on oxygen supply rather than an overloading of intracellular biochemical mechanisms. 5. Perceived exertion in sub-maximal exercise is related to pulse rate as previously described byBorg. However, it is not related to arterial lactate or sensitivity to thermal stress.     

Muscle fibre composition of ratvastus intermedius following immobilisation at different muscle lengths

The knee joints of one hind limb of male Wistar rats (250–300 g) were immobilised in a plaster cast for up to 3 weeks with the limb in either the fully extended or flexed position Serial frozen sections ofvastus intermedius muscle were stained histochemically for myosin ATPase, succinic dehydrogenase, phosphorylase and capillaries. Muscle fibres were classified as either slow twitch oxidative (SO), fast twitch oxidative glycolytic (FOG) or fast twitch glycolytic (FG).Fibre area of SO fibres (3019 ²) decreased by 50% following 3 weeks' immobilisation in the stretched (1532 ²) and shortened (1517 ²) positions. Atrophy of FOG fibres (2456 ²) was greater in muscles immobilised in the stretched (750 ²) than shortened (1185 ²) positions. Evidence has been obtained that muscle fibre number remained unchanged following immobilisation. Control muscles contained 70.4% SO fibres, 29.6% FOG fibres and >0.5% FG fibres. Immobilisation produced an increased proportion of high myosin ATPase staining fibres. The percentage occurrence of FOG fibres increased to 65% and 83% respectively, in muscles immobilised for 3 weeks in the stretched and shortened positions. Mechanisms for the transformation of muscle fibre types and the influence of muscle length on the properties of immobilised muscle are discussed.     

Distribution of skeletofusimotor axons in lumbrical muscles of the monkey

Summary The nerve supply to 25 poles of muscle spindles in the monkey was reconstructed by light microscopy of serial 1-m thick transverse sections of lumbrical muscles. Twenty of 60 motor axons that supplied the spindle poles were identified as skeletofusimotor (). Twenty-eight percent of the spindle poles were innervated by axons, in addition to axons. Every -innervated spindle pole transected an endplate zone of extrafusal muscle. Most axons coinnervated extrafusal fibers rich in mitochondria and the nuclear bag₁ or nuclear chain intrafusal fibers. All but two axons innervated one type of intrafusal fiber only. The intramuscular organization of motor system in lumbrical muscles of the monkey was similar to that of the cat tenuissimus muscle. The function of -innervated spindles may be preferentially to monitor mechanical disturbances arising from the activity of extrafusal muscle units with which they share motor innervation.     

Limiting factors to oxygen transport on Mount Everest 30 years after: a critique of Paolo Cerretelli’s contribution to the study of altitude physiology

In 1976, Paolo Cerretelli published an article entitled Limiting factors to oxygen transport on Mount Everest in the Journal of Applied Physiology . The paper demonstrated the role of cardiovascular oxygen transport in limiting maximal oxygen consumption (O_2max). In agreement with the predominant view of O_2max limitation at that time, however, its results were taken to mean that cardiovascular oxygen transport does not limit O_2max at altitude. So it was argued that the limiting factor could be in the periphery, and muscle blood flow was proposed as a possible candidate. Despite this suggestion, the conclusion generated a series of papers on muscle structural characteristics. These experiments demonstrated a loss of muscle oxidative capacity in chronic hypoxia, and thus provided an unambiguous refutation of the then widespread hypothesis that an increased muscle oxidative capacity is needed at altitude to compensate for the lack of oxygen. This analysis is followed by a short account of Cerretellis more recent work, with a special attention to the subject of the so-called lactate paradox.     

Efficacy of the two-microelectrode voltage clamp technique in crayfish muscle

Crayfish muscle fibres of different dimensions were voltage clamped and white noise current was injected into the fibres at various distances from the voltage clamp current electrode. The clamp current was measured and power spectral densities were calculated. This method revealed the efficacy of the voltage clamp in these fibres. In large fibres (l=1.8–2.0 mm; =100–180m) a space clamp was achieved only for a band width f=40Hz. At a distance of 100m from the clamp electrodes f was 250–500Hz. In fibres of medium size (l=1.0–1.3mm; =60–120m) f was about 80Hz and about 800 Hz at a distance of 100m. In experiments with very small muscle fibres (l=400–600m; =30–50m) f was more than 500Hz. The improvement of the space clamp for the smaller muscle fibres resulted mainly from the reduced total membrane capacity,c _m, of these fibres. The limitations of the space clamp could be derived from the impedance properties of the fibres. The band width of the space clamp correlated with the band width for which the square of the absolute impedance, |Z _p|², of the muscle fibre could be described by a simple RC-model. This correlation was demonstrated in a model circuit.Power density spectra of membrane current fluctuations were measured also. To optimize the resolution of these measurements the contribution of instrumental noise was minimized. The effects of instrumental noise are discussed.This investigation was supported by the Deutsche Forschungs-gemeinschaft     

Activation of the myofibrillar ATPase activity by extension of glycerolextracted insect fibrillar muscle

Summary The myofibrillar ATPase activity of glycerol extracted insect fibrillar muscle fibres (Dorsolongitudinal muscle, Lethocrrus) suspended in ATP-salt solution was determined in dependence of fibre length. Little change occurred between 70 and 100%L ₀. But stretching by only 2–3%L ₀ nearly doubled the ATPase activity and the contractile tension. The proportional increase in tension an ATPase activity in the range of 100–103%L ₀ (30 pmoles ATP split for 1 dyne by 1 cm fibre during 1 min) observed after stretching suggests an increase in the extent of actinmyosin interaction, inspite of the fact that the actin-myosin overlap zone then slightly decreases. The relation between tension increase and ATPase activity increase is nearly the same after stretching or after raising the free calcium concentration; nonetheless, the stretch induced activation is apparently not due to an increase in the calcium affinity of actomyosin (as suggested byChaplain) because stretch activation is observed even at enzyme saturating concentrations of 10^–5 M Ca²⁺. Furthermore the sigmoidal relationship between ATPase activity (or tension) and p Ca and in particular the calcium concentration required for 50% activation is similar in stretched and unstretched fibres, in myofibrils and in actomyosin. The fibre preparation may be stretched in relaxing solution containing less than 10^–8 M Ca⁺⁺ (i.e. in the absence of actin-myosin crosslinking), but the ATPase activity increase following stretching is then only observed after increasing the [Ca⁺⁺] to 10^–7 M; it is correlated with passive tension in relaxing solution rather than with the extent of stretch, suggesting that the element responding to a length change is apparently the passive tension bearing myosin filament which is attached to the Z-line in insect flight muscle.     

Responses of group IV afferent units from skeletal muscle to stretch,contraction and chemical stimulation

Summary In an attempt to differentiate between nociceptive group IV muscle receptors and ergoceptive ones, the discharges of single group IV fibres from skeletal muscle in response to local pressure, sustained stretch, repetitive contraction and intra-arterial injections of bradykinin, 5-hydroxytryptamine (5-HT), potassium, phosphate, and lactate were studied in anaesthetized cats.Of the 75 fibres of the study, 5 units were activated by sustained stretch, the responses occurring with a delay. These stretch-sensitive units could not be activated by local pressure or muscular contraction. Thirteen group IV afferents raised their discharge frequency during repetitive contractions. Some of the units responded immediately with the onset of the contractions, whereas the others showed a pronounced delay.Forty-six units were tested with all or most of the above mechanical and chemical stimuli. In 32 afferents a response to at least one of the stimuli was present. Taking only these units into account, several groups of receptors could be distinguished by their different response combinations. One group was activated by pain-producing substances, but not by muscular activity and thus showed nociceptive properties. Another group showed a raised activity during muscular contractions but did not respond to the algesic agents bradykinin and 5-HT. Units belonging to this group might serve as ergoceptors. The borderline between the two groups was not sharp, a considerable number of group IV afferents was found which had both nociceptive and ergoceptive properties.     

Guinea pig stapedius muscle

Summary Guinea pig stapedius muscle is exceptional among all skeletal and even stapedius muscles of mammals: Muscle size (0.75 mm long, 0.3 mm of maximal diameter) as well as muscle fibres (about 200 m long, about 6 m in diameter) are extremely small, and many characteristics of developing muscle persist up to the adult stage. Quantitative data on blood supply seem to be conflicting: The C/Mf (=capillary to muscle fibre) ratio is extremely low (0.056) in spite of a rather high capillary density (C/mm²=665).Two groups of muscle fibres are distinguished, as well at the ultrastructural level as also by myofibrillar ATPase histochemistry. As compared to other adult fibres, both groups show atypical behaviour and retain, although to a different degree, properties of developing muscle fibres: (1) Myotube like fibres (mlF), about two thirds of the fibre population, show ultrastructural features of myotubes and have centrally located myonuclei. Their mitochondria are in perinuclear and subsarcolemmal, but not in interfibrillar positions. In ATPase histochemistry they correspond to type 2C fibres. (2) Adult type fibres (atF) make up the remaining third of fibres. Their myonuclei are in subsarcolemmal, their mitochondria in typical interfibrillar positions. In ATPase histochemistry they behave like atypical type 1 fibres, as elsewhere only found in developing muscle.In isolated muscle fibres stained for AChE activity, only focal innervation was found. The ultrastructure of the motor endplates was distinctly different: In atF they have long and numerous subsynaptic folds, in mlF they are conspicuous by short and wide subsynaptic folds filled by peculiar axon protrusions. In the depth of the folds of mlF endplates narrowings of the synaptic cleft were found.Based on the discussion of recent literature, the two fibre groups of guinea pig stapedius are supposed to represent two different fibre types, both atypical in adult muscle on account of persisting features of developing muscle, rather than two developmental stages of one and the same type of muscle fibre.Dedicated to Professor Dr. Wolfgang Zenker, Direktor des Anatomischen Institutes der Universität Zürich, on occasion of his 55^th birthdayParts of this study have been the subject of a preliminary presentation and published in abstract form: Burgener, J., Mayr, R.: Morphologisch-histochemische Untersuchungen am M. stapedius des Meerschweinchens. Acta Anat. 105:114 (1979)