Earl Eldred

The effects on spindles of muscle atrophy and hypertrophy

Abstract The effects of decreased and increased use on the morphology, histochemistry and discharge of spindles in the cats medial gastrocnemius muscle were studied in chronic preparations in which one leg either had been immobilized in a cast or the synergist muscles had been denervated. Comparisons were also made of histochemically typed populations of extrafusal fibers in the experimental and the contralateral muscles. The cross-sectional areas of both nuclear bag and chain IF fibers were found to be reduced in the immobilized muscles and increased in the synergists-denervated series relative to the areas in contralateral muscles. Proportionately, however, the changes in IF fibers were less than those found among extrafusal fibers. In the immobilized series the bilateral difference in bag fiber areas was greater than that of the chain fibers, while among extrafusal fibers slow-twitch fibers were affected more than fast-twitch fibers. The discharge of spindle units monitored from dorsal root filaments at resting muscle length was elevated in the immobilized muscles, as was also the stretch sensitivity, i.e., increase in pulse rate per increment of gross muscle stretch. In muscles of the synergists-denervated series the background discharge was increased also, but the effect on stretch sensitivity was not clearly defined.

Postcontraction changes in sensitivity of muscle afferents to static and dynamic stretch

Abstract The effects on dynamic and static components of the afferent stretch response from a muscle were examined in the period after a brief tetanus, which previous study has shown is marked by a persisting elevation in sensory discharge. Afferent activity of the cats triceps surae or medial gastrocnemius muscle was monitored as integrated multiunit discharge in a whole dorsal root, and the ventral roots were stimulated to produced a tetanus. The levels of activity at a static muscle length were found to be elevated in decreasing degree over several millimeters of lengthening beyond that at which the muscle was held during tetanus. During a ramp stretch, the velocity-related overshoot in dorsal root activity was also increased. Such changes were still detected after the elevated discharge had been made to disappear by momentary limited extension of the muscle. They are consistent with the hypothesis of residual effect on the intrafusal fibers, perhaps in the form of persisting actin-myosin crossbridges. Under sinusoidal stretch, the multiunit responses were generally decreased in the first few cycles following tetanus. Observations on single units indicated that the decrease was due chiefly to diminished responses of Ib afferents, which had incompletely recovered from adaptation brought on by excitation during the tetanus.

Response of muscle spindles to stimulation of the sympathetic trunk

Abstract Examination was made for influence of sympathetic innervation on the discharge of receptors of otherwise de-efferented muscle. Firing of units in the cats gastrocnemius was monitored in filaments of dorsal roots while repetitive electrical stimuli were given to the distal stump of one lumbar sympathetic trunk. A characteristic response, consisting of a delayed and gradual acceleration followed by more or less abrupt cessation of firing, was found from both spindle and tendon organ afferents. Blood flow through the leg was markedly reduced during stimulation. This observation and the failure of the full effect to appear when vasoconstriction was blocked, as well as the similarity of the effect to that obtained on the same afferent during compression of the arterial supply, suggest that the response arose mainly as the indirect result of vasoconstriction. Masked by the full response, there may also be a lesser acceleratory effect which was revealed by sympathetic stimulation in the cat under the influence of the adrenergic blocking agent phenoxybenzamine and which was reproduced in some animals by small intra-arterial injections of epinephrine. Slowness in onset of this acceleration following sympathetic stimulation suggests that humoral sensitization of the peripheral endings was the cause, rather than direct motor innervation of intrafusal fibers.

Spindle activity of the tenotomized gastrocnemius muscle in the cat

Abstract Tenotomy of the ankle extensors was performed on one leg in 19 cats, and sensory discharge of the medial gastrocnemius compared with that of the opposite intact muscle in terminal experiments made after postoperative periods of 4–321 days. Levels of discharge of single spindle units were reduced at most positions of ankle extension on the tenotomized side as compared with the intact muscle, both when the spindles were acting passively and when under fusimotor activation. Thus the use of tenotomy as a technique for chronically reducing sensory inflow from spindles is justified. In several muscles examined histologically the spindles appeared slack and even contorted, and this might explain reductions in onset of response when the tenotomized muscle was directly pulled and in the magnitude of afferent discharge induced by succinylcholine. Changes in spindle discharge and configuration that occur following tenotomy appear to be attributable to conditions impressed on the spindle by atrophy of surrounding extrafusal tissue, rather than to intrinsic alterations of the spindle itself.

Metabolic and contractile changes in fast and slow muscles of the cat after glucocorticoid-induced atrophy

Abstract The susceptibility of fast- and slow-twitch hind limb muscles to glucocorticoid-induced atrophy was investigated in adult male cats treated for 10 to 14 days with triamcinolone (4 mg/kg/day), using several histochemical, biochemical, and functional indices. After treatment, muscle weight loss in the fast-twitch muscles (medial gastrocnemius and vastus medialis) occurred to a greater extent than in the slow-twitch muscles (soleus and vastus intermedius), with the latter muscles decreasing in weight proportional to the body weight. Fast-twitch glycolytic (FG) fibers responded with similar degrees of atrophy in the muscles examined; however, slow-twitch oxidative (SO) and fast-twitch oxidative glycolytic (FOG) fibers atrophied more in the fast-twitch compared to the slow-twitch muscles. Phosphofructokinase and NADP+-linked isocitrate dehydrogenase specific activities decreased similarly in the fast-twitch muscles, while no change occurred in the slow-twitch muscles. Functionally, the soleus and medial gastrocnemius remained unchanged in abilities to generate tension tetanically, when this was expressed per unit muscle mass or per unit contractile protein. As a result of the treatment, however, the medial gastrocnemius fatigued faster in response to repetitive stimulation in the glucocorticoid-treated animals. The results suggest that the response of muscle to glucocorticoid-induced atrophy is not regulated by the primary metabolic pathways used for energy production. The differences in response of the SO and FOG fiber types in fast- versus slow-twitch muscles suggest basic differences in metabolic and activity profiles of the same fiber types in different muscles, which may influence susceptibility to atrophy.

Postnatal increase of intrafusal fibers in the rat muscle spindle

Abstract The development of the intrafusal muscle fiber complement in spindles of the extensor digitorum longus and soleus muscles of rats from birth to 12 days of age was studied by radioautographic and conventional microscopic methods. In adult rat muscles an average of 4.08 intrafusal fibers per spindle was found, only 12 units in 83 having more or less than four fibers. On criteria of cross-sectional area of the nucleated and polar regions, and configuration of nuclei at the midlength, the majority of spindles were found to have two fibers of the types known as “nuclear bag” and two “nuclear chain” fibers. A few bag fibers were observed to bifurcate at one motor pole. Spindles from rats killed at birth contained only two intrafusal fibers, one of which was consistently larger in diameter and had many more nuclei than its mate. We concluded that bag and chain fibers were already differentiated at birth. In muscles of 1-day-old rats, a proportion of the spindles showed a split along one end of the smaller intrafusal fiber. By Day 3, half of the spindles had three intrafusal fibers, two of these being of the chain type. Four days after birth, spindles were found in which the large fiber was divided along one end, and by the next day the majority of spindles had four intrafusal fibers. We estimated that the number of nuclei in the equatorial section of a large fiber in the newborn spindle was approximately equal to the sum of nuclei counted in the two bag fibers of spindles in 6-day-old rats. Mitotic figures were not observed during the time of intrafusal fiber multiplication. To further test for the presence of mitosis, radioactive thymidine was injected into 0- to 12-day-old rats, which were killed 8 hours later for serial radioautographic sections. In a given spindle in each muscle, sections were scored for the total number of intrafusal fiber nuclei present and the number of these with labeling. Similar counts were made for the capsule cells. No intrafusal fibers were found with labeled nuclei, although other components of the spindle were labeled. These observations indicate that increase in intrafusal muscle fibers after birth takes place in the rat by simple longitudinal division of the two existing fibers, and that the nuclear complement is determined prior to birth and merely distributed to daughter fibers at the time of division.

Exercise-induced changes of biochemical, histochemical, and contractile properties of muscle in cordotomized kittens

Abstract Characteristics of soleus (SOL) and medial gastrocnemius (MG) muscles in cats cordotomized at either 2 or 12 weeks of age, some of which were exercised on a treadmill during the following 11 to 19 weeks, were compared to see if age at spinalization or if enforced exercise on a treadmill had any differential effects. In non-exercised animals, SOL weights in both 2-week and 12-week groups were less than in 14-week intact controls, but MG weights were equal or greater. Muscles in general were moderately heavier in exercised animals, the MG values in the 12-week animals equalling those in intact adults. The effect of transection was an increase in percent of fast-twitch oxidative-glycolytic fibers in the SOL at the expense of slow-twitch oxidative fibers, and contraction times were shortened. In the MG only a slight shift in fiber-type complement was suggested. Both muscles demonstrated large increases in biochemically determined ATPase activity, without relation to age at cordotomy. Only a modest increase in the myosin ATPase activity as shown biochemically or histochemically was associated with a marked reduction in contraction time in the SOL, whereas in the MG increases in ATPase activity occurred in the absence of a change in contraction time. Because the exercise potentiated the shortening of contraction time in the SOL, characteristic of slow muscle in chronically transected cats, it appears that absence of neuromuscular activity of spinalized cats cannot explain the development of contractile, histochemical, and biochemical properties characteristic of “faster” muscles.

Nature of the persisting canges in afferent discharge from muscle following its contraction.

Publisher Summary This chapter discusses the nature of the persisting canges in afferent discharge from muscle following its contraction. In an experiment presented in the chapter, the postcontraction increase in sensory discharge is observed to study the effects of tenotomy. Several conclusions are drawn from these observations—a persisting increase in discharge at a maintained muscle length and in response to stretch appears after a muscle has undergone contraction, under the condition that the efferent background is otherwise quiet; fusimotor activation alone—that is, contraction of intrafusal fibers, can produce this effect, though extrafusal contraction also seems to contribute; the enhanced discharge, as it is recorded, arises to a major extent in Ia afferent fibers; and the cause of the effect is probably of a mechanical nature. It is believed that the cause of the postcontraction effect is mechanical, rather than due to the sensory ending being affected by a contraction-induced change in the metabolic milieu. Momentary stretch of the muscle results in an immediate disappearance of the postcontraction effect; it is unlikely that this action would rapidly dispel an excess accumulation of metabolite that is capable of such long-lasting effect. The duration of stimulus needed for the response is a few tenths of a second; excitatory levels of K + would probably not build up in this time.

Static stretch sensitivity of Ia and II afferents in the cat's gastrocnemius

The static discharge characteristics of deefferented Ia and II spindle afferents in the cat medical gastrocnemius muscle have been compared with respect to incidence and firing rate of spontaneously firing units, length threshold of non spontaneous units, linearity of the response to stretch, and position sensitivity. Measurements of the stretch response were taken 20 s after each step increase in length so as to obtain the nearly fully adapted rate. Under this condition the frequency-length relationship was quite linear, especially for group II units. The mean position sensitivity of group II fibers exceeded that of I a fibers in the ratio of 1.5∶1.0. The incidence of spontaneously discharging units was about 20% for both types of unit.The relationship between some of these measures and axonal conduction rate were examined. No correlation of position sensitivity with axonal conduction velocity was detected for either afferent type, but the length thresholds of the group II afferents showed a significant trend for slower conducting, that is, smaller fibers to be less sensitive. There was some indication of a direct relationship between conduction velocity and length threshold for I a fibers. The contradiction to the “size principle” and mechanisms contributing to the static discharge behavior of the spindle are discussed.

Comparative study of the actions of nicotine and succinylcholine on the monosynaptic reflex and spindle afferent activity

Summary Nicotine, in low doses of 20–40 μg/kg i.v., blocked the monosynaptic reflex without influencing spindle afferent activity. In contrast, succinylcholine depressed the monosynaptic reflex only when it enhanced spindle discharge. Abolition of the spindle excitatory effect of succinylcholine by gallamine or deafferentation eliminated the monosynaptic reflex depressant action of succinylcholine but did not affect that of nicotine. Mecamylamine, on the other hand, which blocks the nicotinic synapse at the Renshaw cell, abolished the monosynaptic reflex blocking effect of nicotine but not that of succinylcholine. These results emphasize the basically different mechanisms underlying the blockade of the monosynaptic reflex by nicotine and succinylcholine. At intermediate doses of nicotine (40–80 μg/kg i.v.) spindle afferent activity was affected through changes in fusinotor activity consisting of a brief increase followed by prolonged depression. In still higher i.v. doses of nicotine, a direct excitatory effect on the spindle organ was observed. Depression of the monosynaptic reflex through this peripheral effect was revealed when the central action of nicotine was blocked by mecamylamine. Like the action of succinylcholine, it could be blocked by gallamine. Excitation of skin receptors and motor nerve terminals was excluded as a contributory cause of the monosynaptic reflex depression induced by nicotine in the dose range used.