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PubMed2001

Sodium influx during action potential in innervated and denervated rat skeletal muscles.

Resting Na(+) influx (J(i)(Na)) was measured in innervated and denervated (1-6 days) rat extensor digitorum longus muscle in the absence and presence of 2 micromol/L tetrodotoxin (TTX). The mean value of Na(+) permeability (P(Na)) in innervated muscles was 49.6 +/- 2.6 pm.s(-1). At the second day postdenervation, it decreased by about 45%. This was followed, between the second and fourth days, by a sharp rise, which by the sixth day reached a steady value approximately 2.5 times greater than that of innervated muscles. This, most likely, generated the 30% increase in internal [Na(+)] concentration ([Na(+)](I)) observed at this time. Tetrodotoxin reduced P(Na) of both innervated and denervated muscles by about 25%. In 6-day denervated muscles, virtually all the TTX effect on P(Na) represents the blockage of TTX-resistant Na(+) channels. Denervation produced a depolarization of about 20 mV by the sixth day. The extra J(i)(Na) per action potential (AP) decreased monotonically with time after denervation from 20.0 +/- 3.8 in innervated to 11.1 +/- 1.0 nmol.g(-1).AP(-1) in 6-day denervated muscles. The overshoot of the AP decreased from 15 +/- 1 in innervated to 7 +/- 1 mV in 6-day denervated muscles. Likewise, the maximum rate of rise (+dV/dt), an expression of the inward Na(+) current, fell from 305 +/- 14 in innervated to 188 +/- 18 V.s(-1) in 6-day denervated muscles. The estimated 6-day denervated/innervated ratio of peak Na(+) conductance (g(Na)) was 0.67. The changes in AP parameters promoted by denervation were substantially reduced when both innervated and denervated fibers were hyperpolarized to -90 mV. These results suggest that the depolarization, mainly due to the increase in P(Na) /P(K) ratio, increases Na(+) inactivation and consequently reduces peak g(Na), in spite of the absolute increment in resting TTX-sensitive P(Na). This, in addition to the moderate reduction in the inward driving force on Na(+), decreases the inward Na(+) current and the extra J(i)(Na) per AP.

Action Potentials↗
PubMed1976

[Muscle spindles in denervated and reinnervated m. soleus of the rat. II. Changes in the extra- and intrafusal muscle fibers].

After a transient or permanent unilateral denervation of the soleus muscle of the rat changes were investigated of extra- and intrafusal muscle fibres of the denervated (reinnervated) muscle as well as its contralateral still innervated muscle. Those data which were obtained from normal muscles of uninjured rats served as control. The changes of permanent denervated muscles were clear and statistically significant. The extrafusal muscle fibres show a considerable atrophy. The nuclear-chain fibres exhibit a decrease of their calibres. The extent of this atrophy is not as pronounced as in extrafusal muscle fibres. The nuclear-bag fibres show 12 weeks after denervation a small atrophy (or pseudoatrophy) and 18 weeks after denervation a significant hypertrophy. At the same time the number of nuclear-bag fibres is increasing. Besides the increase in number of intrafusal muscle fibres per muscle spindle, a change is observed of proportion of both intrafusal fibre types in favour of nuclear-bag fibres. The hypertrophy and the increase in number of the nuclear-bag fibres are discussed in connection with their functional properties.

Animals↗
PubMed1989

Function and structure of atypical muscle spindles after neonatal nerve crush in rats.

During the early postnatal period, the differentiation and maturation of muscle spindles in the rat is still dependent on their sensory innervation. When a nerve is crushed during this period, most spindles in the denervated muscles degenerate and after reinnervation only occasional spindles of atypical structure are to be found in these muscles. We determined the basic functional properties of these atypical spindles in adult rats and attempted to correlate them with their structural characteristics. The discharge rates of 13 afferent units from the soleus or lateral gastrocnemius muscles were evaluated in response to stretch. These units were capable of a slowly adapting response to 2-4 mm stretches. Their mean discharge frequencies at any point of the ramp-and-hold stretch were, however, on an average 50% lower than normal values. The conduction velocities of afferents from the atypical spindles were in the range of 10-40 m/s. Histological examinations revealed that 90% of the atypical muscle spindles found in the soleus or lateral gastrocnemius muscles had only 1 or 2 intrafusal fibres without any nuclear accumulations as compared to four intrafusal fibres in normal muscle spindles in the rat. The proportional decrease of the discharge rate in both the dynamic and static part of the response of these atypical spindles could be due to the decreased synaptic area between the sensory terminals and the intrafusal fibres and/or to altered structural properties of the intrafusal fibres.

Action Potentials↗
PubMed1988

Effects of calcitonin gene-related peptide on synaptic acetylcholine receptor-channels in rat muscle fibres.

Cultured myotubes and freshly dissociated muscle fibres from adult rats were exposed to calcitonin gene-related peptide (CGRP) and studied by patch-clamp recording during the peptide-induced maximal accumulation of cellular cyclic AMP (cAMP). Acetylcholine receptor- (AChR-) channel properties in myotubes were not modified by the presence of CGRP (10(-7) M). The peptide, applied to the non-patched membrane, significantly increased the variance of the AChR-channel amplitude distribution at the synaptic region of muscle fibres, and three classes of AChR-channels were resolved immediately after peptide application. AChR-channels at extrasynaptic regions of fibres from denervated muscles were unaffected by CGRP. It is suggested that CGRP may regulate the synaptic AChR-channel conductance through second messenger systems.

Animals↗
PubMedDate not supplied

Muscle transposition in the rehabilitation of the paralyzed larynx.

Muscle transposition of the innervated omohyoid muscle into the tendon of the paralyzed posterior cricoarytenoid muscle was studied in a small series of subhuman primates. A similar procedure was described previously by King for treatment of bilateral recurrent nerve injuries. Our studies confirm that this procedure adequately enlarges the airway to allow normal activity without a tracheostomy. Histologic studies appear to show nerve ingrowth occurring at 6 months as in other neuromuscular pedicle procedures. The procedure is easily performed and causes no other muscle denervation.

Animals↗
PubMed1991

Electrical stimulation treatment of dog's denervated orbicularis oculi muscle.

In this investigation, the electrophysiology and pathology of denervated orbicularis oculi muscles have been studied in dogs during chronic electrical stimulation. The orbicularis oculi muscles were unilaterally denervated in 8 dogs, and 4 of these muscles were directly stimulated on a daily basis for 75 days. No difference in minimum stimulus intensities evoking orbicularis oculi muscle twitch contraction appeared between denervated treated and nontreated muscles. A significant reduction of minimum stimulus intensities evoking upper eyelid complete closure (blink), however, was found in the denervated treated muscles between 10 and 30 days (p less than 0.01). At 28 and 75 days, orbicularis oculi muscle biopsies showed no difference in muscle fiber diameter between denervated treated and nontreated muscles. At 75 days, type II muscle fiber distribution, however, was significantly increased in denervated treated muscles compared with denervated nontreated muscles (p less than 0.01). These findings of orbicularis oculi muscle electrophysiology were consistent with a transient reversal of denervation changes by electrical stimulation, partially supported by muscle biopsies.

Animals↗
PubMed1977

Blood flow and uptake of glucose and amino acids in ischemic muscle.

In order to examine muscle ischemia, muscle blood flow in the rat hindlimb was decreased by vessel ligation. Amino acid uptake, studied with [14C]alpha-aminoisobutyric acid, was decreased in ischemic Type I (soleus) muscle. Glucose uptake, studied with [14C]deoxyglucose, was increased in Type I muscle. These changes were temporally associated with histologic changes of ischemia in soleus muscle. Denervation, atrophy, and hypertrophy also produced uptake changes with these techniques, and although more prominent in soleus, the changes were also seen in Type II muscle.

Absorption↗
PubMed1986

Effects of actinomycin D on contractile properties of denervated rat skeletal muscle.

We studied the mechanical and electrical properties in the extensor digitorum longus muscle of Wistar rats in vitro 4 days after denervation. In a group of animals, actinomycin D was injected intravenously at the time of denervation. The prolongation of contraction and relaxation time, and the increase in twitch tension observed in denervated muscles were prevented by the drug. Other denervatory changes such as the elimination of cooling potentiation, posttetanic potentiation, staircase phenomenon, and shortening of caffeine contracture were also inhibited or partially reverted by actinomycin D. In addition, some electrical denervatory changes such as the decrease of resting membrane potential and slowing of maximum rate of fall of the action potential were partially abolished by actinomycin D. These results support the hypothesis that a new synthesis of proteins is related to denervation changes.

Animals↗
PubMed1990

Competitive mechanisms underlying synapse elimination in the lumbrical muscle of the rat.

The process of neuromuscular synapse elimination has been studied in the fourth deep lumbrical (4DL) muscle of the rat, a preparation which offers technical advantages for some types of experimental work. Studies have been performed both during development and in adult denervated muscles undergoing reinnervation. Results indicate that synapse elimination is dependent upon competition between motoneurons. Cellular mechanisms underlying this competition have also been explored. Both neuromuscular activity and muscle fiber type recognition appear to play a role, but positional cues appear unimportant in this small muscle.

Animals↗
PubMed1981

[Changes in the sensitivity of the muscle spindles of fast and slow-contracting muscle fibers following chronic deafferentation].

The activity of muscle spindles was investigated in fast (m. EDL) and slow (m. sol) muscles of the cat 2-5 weeks after chronic deefferentation. The spontaneous activity of spindles in both muscles remains unchanged. The background activity and activity in dynamic and static phases of stretching both in primary and in secondary endings was much in chronic denervated muscle than in control. This increase in spindle activity was more pronounced in the slow muscle.

Muscle Contraction↗
PubMed1996

Nitric oxide synthase is concentrated at the skeletal muscle endplate.

NO performs a wide array of cell signaling functions. Neuronal NO synthase (nNOS) immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (NDP) activity, a marker of nNOS, were concentrated at adult rat neuromuscular junctions and persisted in denervated muscle indicating the localization of the enzyme to the postsynaptic surface. The concentration of nNOS at the muscle endplate suggests NO could serve as a messenger pre- and postsynapticly.

Animals↗
PubMed1986

Improved motor response due to chronic electrical stimulation of denervated tibialis anterior muscle in humans.

Nine patients with complete denervation of the tibialis anterior were admitted to a stimulation program in order to restore dorsiflexion of the foot. Best results were obtained with pulses of 20-msec pulse width and 20-msec interval. After 3 weeks of training for 2 X 20 min/day, dorsiflexion due to stimulation was increased in all patients. In some of them, gait could be improved during the swing phase using electrical stimulation. The applied training program thus reversed the course of disuse atrophy and proved the feasibility of functional electrical stimulation for patients with denervated muscles.

Adult↗
PubMed1981

[Neurotrophic control of the resting membrane potential of phasic muscle fibers in frogs].

Muscle denervation or blockade of axoplasmic transport by colchicine with no impairment of neuro-muscular transmission, cause a decrease of the resting membrane potential (RMP) of muscle fibers in frogs. Administration of actinomycin D or puromycin does not affect the development of depolarization in muscle fibers under these conditions. Ouabain does not change the RMP of muscle fibers, which indicates to small amount of "pumping" current in the RMP. Adrenaline, insulin, dibutyryl c. AMP, theophylline hyperpolarize the muscle fiber membrane in denervated and intact muscles. Ouabain abolishes this effect. The fiber RMP in denervated and colchicine treated muscles in potassium-free Ringer solution is lower than in intact muscles under similar conditions. The mechanism of postdenervation depolarization of muscle fibers seems to depend on decrease in the intact intracellular potassium concentration as a result of Na+, K+-pump diminished activity. Neurotrophic control of muscle fibers RMP in frog depends on the substances supplied by axoplasmic flow.

Animals↗
PubMed1999

Neuromuscular function of the latissimus dorsi muscle in goats after dynamic cardiomyoplasty.

Skeletal muscle deterioration is emerging as a limitation to long-term cardiac assist by dynamic cardiomyoplasty. Chronic electrical stimulation of in situ skeletal muscle showed that ischemia, decreased muscle preload, muscle overuse, and chronic electrical stimulation are factors for muscle deterioration. Transposition around the heart has been associated with signs of muscle denervation after chronic electrical stimulation. To evaluate latissimus dorsi muscle neuromuscular function after longterm dynamic cardiomyoplasty, we performed neuromuscular functional analysis and histology on the latissimus dorsi muscle and thoracodorsal nerve of six normal goats and six goats after 6 months of dynamic cardiomyoplasty. Electromyographic analysis showed positive sharp waves and fibrillation potentials in the latissimus dorsi of three goats from the dynamic cardiomyoplasty group. Conduction velocity of the thoracodorsal nerve of goats from the dynamic cardiomyoplasty group (58.32+/-9.80 m/s) was reduced compared to the goats from the control group (71.48+/-5.71 m/s, P = 0.02). Histologic changes in skeletal muscle were compatible with denervation. Loss of myelin sheaths, collapse of endoneurial connective tissue, and solitary foci of axonophagia and myelinophagia further documented severe injury to the thoracodorsal nerve in goats from the dynamic cardiomyoplasty group. The latissimus dorsi muscle wrap was denervated after long-term dynamic cardiomyoplasty. Traction on the neurovascular pedicle at each contraction of the transposed muscle may induce afferent axonal injury of the thoracodorsal nerve resulting in diminished muscular function.

Animals↗
PubMed1993

Properties of acetylcholine receptors in adult rat skeletal muscle fibers in culture.

The distribution and biophysical properties of acetylcholine receptors were studied, using morphological and patch-clamp techniques, in adult rat skeletal muscle fibers dissociated by collagenase and maintained in culture. Up to ten hours after dissociation, there were no changes in either the distribution or the biophysical properties of junctional acetylcholine receptors. In long-term culture (5 to 14 days), a new type of acetylcholine receptor was inserted all over the muscle fibers; the channel properties were characterized by a longer open time and a smaller conductance, similar to what has been observed in in vivo denervated muscles. Using autoradiography, we found that during culture an impaired incorporation of new acetylcholine receptors in the former endplates caused a progressive decrease in the density of junctional acetylcholine receptors. This contrasts with muscle fibers denervated in vivo, where the density of receptors does not change after denervation.

Animals↗
PubMed1981

Increased muscle calcium. A possible cause of mitochondrial dysfunction and cellular necrosis in denervated rat skeletal muscle.

Mitochondrial preparations derived from denervated rat skeletal muscle and paired controls were characterized with respect to their ability to take up externally added Ca2+. The denervated and control muscle homogenates and mitochondrial [Ca2+] were also determined. Our data indicate that the denervated mitochondria are able to take up less Ca2+ than the controls before uncoupling occurs. This defect is associated with elevated [Ca2+] in homogenate and mitochondrial fractions in the denervated state. The causal relationship between Ca2+ overload, mitochondrial functional damage and cell necrosis is discussed.

Animals↗
PubMed1999

Cytosolic citrate and malonyl-CoA regulation in rat muscle in vivo.

In liver, insulin and glucose acutely increase the concentration of malonyl-CoA by dephosphorylating and activating acetyl-CoA carboxylase (ACC). In contrast, in incubated rat skeletal muscle, they appear to act by increasing the cytosolic concentration of citrate, an allosteric activator of ACC, as reflected by increases in the whole cell concentrations of citrate and malate [Saha, A. K., D. Vavvas, T. G. Kurowski, A. Apazidis, L. A. Witters, E. Shafrir, and N. B. Ruderman. Am. J. Physiol. 272 (Endocrinol. Metab. 35): E641-E648, 1997]. We report here that sustained increases in plasma insulin and glucose may also increase the concentration of malonyl-CoA in rat skeletal muscle in vivo by this mechanism. Thus 70 and 125% increases in malonyl-CoA induced in skeletal muscle by infusions of glucose for 1 and 4 days, respectively, and a twofold increase in its concentration during a 90-min euglycemic-hyperinsulinemic clamp were all associated with significant increases in the sum of whole cell concentrations of citrate and/or malate. Similar correlations were observed in muscle of the hyperinsulinemic fa/fa rat, in denervated muscle, and in muscle of rats infused with insulin for 5 h. In muscle of 48-h-starved rats 3 and 24 h after refeeding, increases in malonyl-CoA were not accompanied by consistent increases in the concentrations of malate or citrate. However, they were associated with a decrease in the whole cell concentration of long-chain fatty acyl-CoA (LCFA-CoA), an allosteric inhibitor of ACC. The results suggest that increases in the concentration of malonyl-CoA, caused in rat muscle in vivo by sustained increases in plasma insulin and glucose or denervation, may be due to increases in the cytosolic concentration of citrate. In contrast, during refeeding after starvation, the increase in malonyl-CoA in muscle is probably due to another mechanism.

Acetyl-CoA Carboxylase↗
PubMed1986

Canine experimental free muscle transplantation.

Transplants of the cranial portion of the dog sartorius muscle were able to generate 70% of control force after 3 months if the artery, vein, and nerve were reanastomosed. Our histological and histochemical findings correlate with the functional findings. In a separate group of animals that had their muscles denervated prior to replantation, no collateral sprouting was noted and no function could be recorded when the nerve was stimulated proximally. These findings suggest that clinical application of free muscle transplantation is strongly supported by this animal model if due consideration is paid to surgical procedure and anatomical structure.

Animals↗