Metabolic adaptations to training precede changes in muscle mitochondrial capacity.

To determine whether increases in muscle mitochondrial capacity are necessary for the characteristic lower exercise glycogen loss and lactate concentration observed during exercise in the trained state, we have employed a short-term training model involving 2 h of cycling per day at 67% maximal O2 uptake (VO2max) for 5-7 consecutive days. Before and after training, biopsies were extracted from the vastus lateralis of nine male subjects during a continuous exercise challenge consisting of 30 min of work at 67% VO2max followed by 30 min at 76% VO2max. Analysis of samples at 0, 15, 20, and 60 min indicated a pronounced reduction (P less than 0.05) in glycogen utilization after training. Reductions in glycogen utilization were accompanied by reductions (P less than 0.05) in muscle lactate concentration (mmol/kg dry wt) at 15 min [37.4 +/- 9.3 (SE) vs. 20.2 +/- 5.3], 30 min (30.5 +/- 6.9 vs. 17.6 +/- 3.8), and 60 min (26.5 +/- 5.8 vs. 17.8 +/- 3.5) of exercise. Maximal aerobic power, VO2max (l/min) was unaffected by the training (3.99 +/- 0.21 vs. 4.05 +/- 0.26). Measurements of maximal activities of enzymes representative of the citric acid cycle (succinic dehydrogenase and citrate synthase) were similar before and after the training. It is concluded that, in the voluntary exercising human, altered metabolic events are an early adaptive response to training and need not be accompanied by changes in muscle mitochondrial capacity.

Auditory brain stem of the ferret: some effects of rearing with a unilateral ear plug on the cochlea, cochlear nucleus, and projections to the inferior colliculus.

To examine the influence of acoustic experience on the development of the mammalian auditory brain stem, darkly pigmented ferrets were reared with a plug inserted in the right outer ear. The plugs were first inserted on postnatal day 23-34 and produced a variable, frequency-dependent attenuation of up to 60 dB. Between 3-15 months after the ear plug was begun, animals were prepared for physiological recording and injection of wheat germ agglutinin-HRP (WGA-HRP) in the left inferior colliculus (IC). The plug was removed and the condition of the right ear was assessed by pure-tone stimulation and recordings from neurons in the left IC. Neural audiograms for each animal showed a residual deficit in most cases. Following 24-60 hr survival, the animals were perfused and the right ear was examined. Brain-stem sections were reacted with tetramethylbenzidine. Outer and/or middle ear pathology was present in over half of the animals. However, the cochleas appeared to be normal and the spiral ganglion cells were normal by several quantitative criteria: number, area, and nucleolar eccentricity. The volume of each division of the cochlear nuclei (CN) and the areas of individual neurons in the anteroventral CN were the same on the right and left sides. The number of CN neurons retrogradely labeled from the left IC injection of WGA-HRP was found to be significantly increased in the left CN, relative to normal animals, when expressed as a ratio of the number labeled in the right CN. We conclude that the residual hearing loss in the previously plugged ears was predominantly or exclusively conductive. Neonatal, unilateral conductive hearing loss in the ferret does not lead to degeneration of the CN on the side of the loss, but it does lead to at least one rearrangement of auditory brain-stem connectivity. We suggest that the extent to which the brain stem is modified by early auditory deprivation is dependent on the type, degree, and symmetry of the hearing loss.

An anomaly in the auditory brain stem projections of hypopigmented ferrets.

The number of cochlear nucleus (CN) neurones projecting to the ipsi- and contralateral inferior colliculus (IC) was studied in darkly pigmented and hypopigmented ferrets by the retrograde transport of wheat germ agglutinin-horseradish peroxidase. The contralateral projection in all divisions of the CN of both albino and 'red eyed' ferrets was normal. However, the ipsilateral projection from the anteroventral CN was significantly smaller in albino than in pigmented ferrets. The volume of each division of the CN was also measured and was found to be the same in albinos as in pigmented animals. The results show that hypopigmented ferrets have at least one anomaly among the connections of the auditory brain stem.

Auditory brainstem of the ferret: effects of unilateral cochlear lesions on cochlear nucleus volume and projections to the inferior colliculus.

Unilateral lesions of the right cochlea were made in ferrets aged postnatal day (P)12 to P93. The extent of the lesions was assessed by counting remaining hair cells and ganglion cells in midmodiolar sections through the lesioned cochleas and by comparison with a sample of unlesioned cochleas. The neural effects of the lesions were assessed by measuring the volume of each cochlear nucleus (CN) and by counting the number of neurons in each CN that were retrogradely labeled following injections of WGA-HRP in the left inferior colliculus (IC). Survival times between lesioning and injection of the tracer ranged from 11 to 98 days. CN volume and projections to the IC were also measured in a sample of normal adult ferrets and in normal infants aged P39 to P80. Cochlear lesions resulted in a reduction of the volume of the CN on the lesioned side, relative to the other CN, in animals of all ages and survival times. The extent of the CN volume reduction was negatively correlated with the number of remaining cochlear ganglion cells. However, even where the number of ganglion cells was within the normal range, significant volume reductions occurred. The ventral CN was more severely affected by the lesions than the dorsal CN, but no difference was found between the anteroventral and posteroventral divisions of the nucleus. There was no significant difference in the extent of CN volume reductions between animals of different ages or survival times. Lesions of the right cochlea in younger animals (P14 to P24) resulted, after 90 days survival, in an increase in the number of left CN neurons projecting to the left IC. No significant increase was seen following lesions in older (P90) ferrets or following short (11 or 30 days) survival times in young (P14 to P24) ferrets. The extent of the increase in the ipsilateral CN-IC projection was not related to the number of remaining ganglion cells or to the division of the CN examined. Lesions did not affect the contralateral CN-IC projection. We conclude that cochlear lesions in infant ferrets can alter auditory brainstem morphology and connectivity. The dependence of these alterations on the age of the animal, survival time following lesion, and extent of the lesion varies markedly with the index examined.

Effects of impulse blockade on the contractile properties of rat skeletal muscle.

1. Pressure was used to produce a localized block of impulse conduction in motor nerve fibres supplying rat plantaris and soleus muscles. After 1 week of inactivity both muscles exhibited marked atrophy of type I and type II muscle fibres. 2. In treated plantaris and soleus muscles the specific tetanic tensions were reduced to approximately half those of untreated control muscles; the specific twitch tensions were unchanged. The fall in specific tetanic tension in the nerve-blocked muscles was not associated with impaired excitation of muscle fibres during repetitive stimulation. 3. In nerve-blocked plantaris muscles the contraction and half-relaxation times became significantly prolonged whereas no change could be demonstrated in similarly treated soleus muscles. In both muscles the maximum rates of tetanic tension development increased following nerve block. 4. It is concluded that, in the rat, most of the changes in contractile properties and in muscle fibre size which follow denervation may be attributed to disuse rather than to interruption of axoplasmic transport.

Contrasting effects of suspension on hind limb muscles in the hamster.

The contractile properties of plantaris and soleus muscles were studied in 46-day-old hamsters after 4 weeks of rear-end suspension; their controls were animals which had not been treated or else had been operated upon but not suspended. In the suspended hamsters the plantaris muscles, of which approximately 90% of fibers are normally type II, maintained the properties of fast-twitch muscles in terms of their contraction and half-relaxation times, maximum rates of rise of tetanic tension, and posttetanic potentiation of the twitch. The small reduction of mean tetanic tension, although not significant statistically, was compatible with relatively mild atrophy of the type II fibers; approximately half of the type I fibers appeared to have converted to type II. In contrast, the soleus muscles, normally slow-twitch with approximately 60% type I fibers, exhibited significant shortening of their contraction and half-relaxation times after suspension and the maximum rates of rise of tetanic tension were increased. These changes, and the greatly reduced twitch and tetanic tensions, were compatible with the finding of much greater atrophy of type I than type II fibers, together with the conversion of approximately 10% of fibers from type I to type II. Unlike other contractile variables, posttetanic depression of the soleus twitch was unaffected by suspension. Our findings have implications in relation to other models of disuse.

Physiologic and histologic features of muscle development in the hamster.

This study determined to what extent the hind limb muscles of hamsters resemble those of other mammals in undergoing changes in physiologic, morphologic, and histochemical properties as a function of age. Maximal isometric twitch and tetanic responses were evoked in soleus and plantaris muscles of hamsters aged 13 days to 6 months; all experiments were conducted in vivo under sodium pentobarbital anesthesia. In keeping with findings in the cat and rat, both hamster muscles had relatively prolonged twitches in the youngest animals; the twitches became briefer during development, that of plantaris having a minimum mean contraction time of 15.4 +/- 2.4 ms at 20 days and that of soleus, 28.3 +/- 3.5 ms at 46 days. In both muscles there was a subsequent slight prolongation of the twitch. The two muscles had similar masses at 13 and 20 days; thereafter the plantaris became considerably larger and stronger than the soleus and developed more tetanic tension per unit cross-sectional area. In keeping with its briefer contraction, plantaris had a more rapid rate of rise of tetanic tension than soleus and was more susceptible to fatigue; whereas the soleus developed depression of the twitch after a tetanus, the plantaris exhibited potentiation. Histological and histochemical studies showed that the plantaris had significantly more muscle fibers than the soleus and a much greater proportion of type II fibers (91 and 39%, respectively, in 120- to 180-day-old animals). Whereas the type II fibers had similar cross-sectional areas in the two muscles, the type I fibers were significantly smaller in plantaris than in soleus.

Absence of fibrillation after muscle injury.

The possibility was examined that fibrillation potentials may occur in those parts of muscle fibers which become functionally denervated following segmental necrosis. Focal necrotic lesions were induced in rat semitendinosus muscles by crushing, ligating, or cutting muscle fibers. When the treated muscles were examined microscopically and recordings made with intracellular or extracellular electrodes, fibrillations were found to be either completely absent or extremely infrequent. Fibrillation potentials were also absent in the brachioradialis muscle of a human subject after myotomy. In contrast to these negative results, surgical denervation of the rat semitendinosus induced fibrillation activity within 3 days; when fully developed, fibrillations occurred in approximately one-half of the fibers at any time. The findings are considered to have significance for an understanding of the pathogenesis of those "myopathic" disorders in which fibrillations are found.