Golgi complex, endoplasmic reticulum exit sites, and microtubules in skeletal muscle fibers are organized by patterned activity.
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The Golgi complex of skeletal muscle fibers is made of thousands of dispersed elements. The distributions of these elements and of the microtubules they associate with differ in fast compared with slow and in innervated compared with denervated fibers. To investigate the role of muscle impulse activity, we denervated fast extensor digitorum longus (EDL) and slow soleus (SOL) muscles of adult rats and stimulated them directly with patterns that resemble the impulse patterns of normal fast EDL (25 pulses at 150 Hz every 15 min) and slow SOL (200 pulses at 20 Hz every 30 sec) motor units. After 2 weeks of denervation plus stimulation, peripheral and central regions of muscle fibers were examined by immunofluorescence microscopy with regard to density and distribution of Golgi complex, microtubules, glucose transporter GLUT4, centrosomes, and endoplasmic reticulum exit sites. In extrajunctional regions, fast pattern stimulation preserved normal fast characteristics of all markers in EDL type IIB/IIX fibers, although inducing changes toward the fast phenotype in originally slow type I SOL fibers, such as a 1.5-fold decrease of the density of Golgi elements at the fiber surface. Slow pattern stimulation had converse effects such as a 2.2-fold increase of the density of Golgi elements at the EDL fiber surface. In junctional regions, where fast and slow fibers are similar, both stimulation patterns prevented a denervation-induced accumulation of GLUT4. The results indicate that patterns of muscle impulse activity, as normally imposed by motor neurons, play a major role in regulating the organization of Golgi complex and related proteins in the extrajunctional region of muscle fibers. (+info)
Increased neuromuscular activity reduces sprouting in partially denervated muscles.
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The effects of increasing neural activity on sprouting remain unclear and controversial. In a rat model of partial denervation of skeletal muscles, we investigated the effect of neuromuscular activity on sprouting. Rat hindlimb muscles were partially denervated by avulsion of either L4 or L5 spinal root. Immediately after partial denervation, the rats were divided into three groups: (1) normal caged activity, (2) running exercise on wheels, 8 hr daily, and (3) functional electrical stimulation (FES) of sciatic nerves, 20 Hz for 8 hr daily. At 1 month, muscle unit (MU) enlargement was quantitated electrophysiologically and histochemically. MU twitch force was increased by four- to fivefold by partial denervation in extensively denervated tibialis anterior (TA) and medial gastrocnemius (MG) and by approximately twofold in moderately denervated plantaris (PL) and soleus (SOL). For the extensively denervated TA and MG muscles, MU enlargement, measured electrophysiologically, declined significantly after an average of 1757 +/- 310 m/d running exercise and daily FES for 1 month. The detrimental effects on MU enlargement were much less but significant in the moderately denervated PL and did not reach statistical significance in the moderately denervated SOL muscle. Histochemical evaluation of sprouting showed a reduction in the number of sprouts in the extensively denervated TA muscle, but not the moderately denervated PL and SOL muscles, by increased neuromuscular activity. Thus, increased neuromuscular activity is detrimental primarily in muscles that are extensively denervated, and the MUs are smaller than under conditions in which the muscles experience normal physiological levels of activation. (+info)
Baroreceptor reflex effects on transient and steady-state hemodynamics of salt-loading hypertension in dogs.
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Intact dogs were compared with barorecptor-denervated dogs to determine the extent to which the baroreceptor reflexes delay the onset and offset transients and alter the final steady-state levels of salt-loading hypertension. Two months after their renal mass had been reduced to about one-third of normal, hypertension was produced in both groups of dogs by continuous intravenous infusion of isotonic saline (190 ml/kg day-1). Major hemodynamic variables were recorded continuously 24 hours/day throughout the experimental period. Both groups of dogs had similar control 24-hour arterial blood pressure values: intact dogs averaged 112 plus or minus 4.1 (SE) mm Hg, and denervated dogs averaged 110 plus or minus 4.3 mm Hg. Both groups reached the same average plateau of elevated arterial blood pressure: intact dogs averaged 142 plus or minus 4.8 mm Hg, and denervated dogs averaged 142 plus or minus 8.7 mm Hg. After the start of salt loading, the denervated dogs reached their plateau level of arterial blood pressure in an average of 8 hours compared with nearly 24 hours for the intact dogs. Cardiac output also rose more rapidly in the denervated dogs and reached a maximum elevation of 26% above the control level in an average of 7.4 hours compared with a maximum elevation of 40% above control in the intact dogs in 18 hours. Total peripheral resistance fell below the control level during the entire first day of infusion in the intact dogs but was somewhat elevated in the denervated dogs. When the saline infusion stopped, arterial blood pressure in both groups returned to control levels within 24 hours. The results indicate that the major action of the baroreceptor reflexes on the onset of salt-loading hypertension is to slow the development of hypertension by modifying the total peripheral resistance; the final steady-state level of hypertension is unaffected by the baroreceptor reflexes. (+info)
Lipoprotein lipase activity in skeletal muscles of the rat: effects of denervation and tenotomy.
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The effects of denervation, tenotomy, or tenotomy with simultaneous denervation on the activity of heparin-releasable and intracellular, residual lipoprotein lipase (LPL) and triacylglycerol (TG) content were examined in rat skeletal muscles. An influence of muscle electrostimulation on denervated and tenotomized muscles was also evaluated. Activity of both LPL fractions was decreased in denervated and/or tenotomized soleus and red portion of gastrocnemius muscles. It was accompanied by a slight elevation of the intracellular TG content. Electrostimulation increased activities of both fractions of LPL in red muscles from intact hindlimbs. In stimulated denervated muscles without or with simultaneous tenotomy, activity of two LPL fractions was also enhanced, but control values were reached only in denervated soleus muscle. Electrical stimulation had no pronounced effect on LPL activity in tenotomized muscles. In conclusion, denervation and/or tenotomy decreases LPL activity in red muscles, indicating reduction of the muscle potential to utilize circulating TG. Electrostimulation only partly restores the diminished LPL activity in denervated muscles, without any effect in tenotomized ones. Thus, to maintain LPL activity in resting muscle, intact innervation and tension are needed. (+info)
Effects of short-term denervation and subsequent reinnervation on motor endplates and the soleus muscle in the rat.
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The rat sciatic nerve was locally frozen, and changes in the nerve, motor endplates, and the soleus muscle were examined for up to 6 weeks by light and electron microscopy. The wet weights of denervated soleus muscles compared with contralateral values progressively declined to a minimum at 2 weeks after injury (60.7 +/- 2.5%) and began to reverse following 3 weeks. The sciatic nerve thoroughly degenerated after freezing. However, numerous regenerated myelinated and thin nerve fibers were observed at 3 weeks. They were considerably enlarged but still smaller than normal counterparts at 6 weeks postoperatively. Nerve terminals containing synaptic vesicles of endplates disappeared at day 1 and mostly reappeared at 3 weeks (about 70% of the endplates). All endplates examined were reinnervated at 4, 5, and 6 weeks. On the other hand, postsynaptic folds of muscle fibers seemed to be only slightly influenced by denervation or reinnervation. Ultrastructural alterations of myofibrils, in particular the loss of register, immediately appeared after denervation, spread progressively, peaked at 2 weeks, ameliorated following reinnervation, and became significantly normalized at 6 weeks after freezing. The proportion of type II fibers in the soleus muscle similary showed an increase and a decrease with a short delay in response to denervation and reinnervation, respectively. This study clearly demonstrated that the nerve supply affects the ultrastructural integrity of skeletal muscles. In addition, changes in the endplates and the soleus muscle evaluated in this study after short-term denervation are largely reversible following reinnervation. (+info)
Both central command and exercise pressor reflex reset carotid sinus baroreflex.
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In decerebrate unanesthetized cats, we determined whether either "central command," the exercise pressor reflex, or the muscle mechanoreceptor reflex reset the carotid baroreflex. Both carotid sinuses were vascularly isolated, and the carotid baroreceptors were stimulated with pulsatile pressure. Carotid baroreflex function curves were determined for aortic pressure, heart rate, and renal vascular conductance. Central command was evoked by electrical stimulation of the mesencephalic locomotor region (MLR) in cats that were paralyzed. The exercise pressor reflex was evoked by statically contracting the triceps surae muscles in cats that were not paralyzed. Likewise, the muscle mechanoreceptor reflex was evoked by stretching the calcaneal tendon in cats that were not paralyzed. We found that each of the three maneuvers shifted upward the linear relationship between carotid sinus pressure and aortic pressure and heart rate. Each of the maneuvers, however, had no effect on the slope of these baroreflex function curves. Our findings show that central command arising from the MLR as well as the exercise pressor reflex are capable of resetting the carotid baroreflex. (+info)
Effect of unilateral denervation on maximum specific force in rat diaphragm muscle fibers.
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We hypothesize that 1) the effect of denervation (DNV) is more pronounced in fibers expressing fast myosin heavy chain (MHC) isoforms and 2) the effect of DNV on maximum specific force reflects a reduction in MHC content per half sarcomere or the number of cross bridges in parallel. Studies were performed on single Triton X-100-permeabilized fibers activated at a pCa (-log Ca2+ concentration) of 4.0. MHC content per half sarcomere was determined by densitometric analysis of SDS-PAGE gels and comparison to a standard curve of known MHC concentrations. After 2 of wk DNV, the maximum specific force of fibers expressing MHC2X was reduced by approximately 40% (MHC(2B) expression was absent), whereas the maximum specific force of fibers expressing MHC2A and MHC(slow) decreased by only approximately 20%. DNV also reduced the MHC content in fibers expressing MHC2X, with no effect on fibers expressing MHC2A and MHC(slow). When normalized for MHC content per half sarcomere, force generated by DNV fibers expressing MHC2X and MHC2A was decreased compared with control fibers. These results suggest the force per cross bridge is also affected by DNV. (+info)
Role of cardiac nerves in the cardiovascular response to cocaine in conscious dogs.
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BACKGROUND: Although the cardiovascular toxicity of cocaine is well recognized, considerable controversy remains as to the relative contribution of local norepinephrine reuptake inhibition versus central stimulatory effects of cocaine in eliciting its cardiovascular actions. The purpose of the present study was to determine the role of cardiac nerves in mediating the left ventricular (LV) and coronary hemodynamic responses to cocaine. METHODS AND RESULTS: We studied the cardiovascular response to acute cocaine administration (1 mg/kg) in 10 intact, conscious dogs and 6 dogs with ventricular denervation (VD). There were no significant differences in baseline hemodynamic parameters or plasma catecholamines between the 2 groups. In response to acute cocaine, LV and coronary hemodynamic responses were enhanced in the VD dogs. The enhanced systemic pressor and heart rate responses in VD dogs suggest that cardiac nerves mitigate the response to cocaine through ventricular mechanoreceptors rather than mediating the responses. CONCLUSIONS: These data suggest that peripheral blockade of norepinephrine reuptake is not the principal mechanism of the acute cardiac effects of cocaine. Rather, cardiac nerves modulate the effects of cocaine through baroreflex mechanisms. Thus, individual differences in baroreflex sensitivity may explain the hemodynamic variability observed in response to cocaine. (+info)