Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The mechanical properties of motor units of the cat superior oblique muscle and axonal conduction velocities of trochlear motoneurons have been studied at several postoperative times after intracranial axotomy of the trochlear nerve. 2. Whole muscle twitch forces were generally within the normal range by approximately 4 mo postoperative, indicating that reinnervation is complete at this time. 3. Among animals studied 3.5-4.5 months after trochlear axotomy, average motor-unit tetanic forces were increased by a factor of approximately 2.5 compared with units studied in normal superior oblique muscle. Average motor-unit tetanic forces in animals studied 14.5-23 mo after axotomy were also increased relative to normal, but the difference was not significant. Among all reinnervated motor units, there was a tendency for increased twitch time-to-peak relative to control. Reinnervated motor-unit fatigue properties were similar to normal. 4. Average trochlear motoneuron conduction velocities for animals at all postoperative intervals remained significantly lower than the average conduction velocities from three of four normal animals. 5. Counts of Nissl-stained cell bodies in axotomized and control, contralateral trochlear nuclei showed that some cell loss had occurred, averaging approximately 17% 3.5-4.5 mo postoperative and 24% 14.5-23 mo postoperative. Associated with this loss was an increase (10%) of axotomized motoneuron soma cross-sectional area. 6. Muscle fiber cross-sectional areas (CSA) were measured in reinnervated superior oblique muscles and compared with CSAs from contralateral, control muscles. Average CSA was significantly decreased in all reinnervated muscles, with the relative decreases ranging from approximately 10 to 28%. 7. The results are discussed in terms of factors that determine motor-unit force; muscle fiber CSA, specific force, and innervation ratio. We conclude that the increases of average motor-unit force in short-term reinnervated superior oblique muscles are most likely related to polyneuronal innervation of muscle fibers and that the return of these forces to normal levels in long-term muscles is related to synapse elimination. Our results are compared with those of other self-reinnervation studies, and the potential role played by the time muscle remains denervated in determining the persistence of polyneuronal innervation after reinnervation is considered.
 ...
PMID:Properties of motor units after self-reinnervation of the cat superior oblique muscle. 874 93

1. The purpose of this study was to determine the role of motor unit remodelling in the deficit that develops in the maximum isometric tetanic force (Fo) of whole medial gastrocnemius (MGN) muscles in old compared with adult rats. The Fo values and morphological data were determined for MGN muscles and eighty-two single motor units in muscles of adult (10-12 months) and sixty-two units in those of old (24-26 months) F344 rats. During an unfused tetanus, fast and slow (S) motor units were identified by the presence and absence of sag, respectively. Fast-fatigable (FF) and fast-fatigue-resistant (FR) units were classified by fatigue indices less than or greater than 0.50, respectively. 2. For old rats, whole MGN muscle Fo was 29% less than the value of 11.2 N measured for adult rats. The deficit in whole muscle Fo of old rats resulted from equivalent decreases in the number of motor units, 16% smaller than the adult value of ninety-seven, and in the mean motor unit Fo value, 14% less than the adult value of 117 mN. 3. With ageing, little motor unit remodelling occurred in FR units, whereas the S and FF motor units demonstrated dramatic, but opposing, changes. For S units, the number of units remained constant, but the number of fibres per motor unit increased 3-fold from 57 to 165. In contrast, the number of FF units decreased by 34% and the number of fibres per motor unit of the remaining units decreased to 86% of the adult value of 333. The age-related remodelling of motor units appeared to involve denervation of fast muscle fibres with reinnervation of denervated fibres by axonal sprouting from slow fibres.
 ...
PMID:Properties of single motor units in medial gastrocnemius muscles of adult and old rats. 878 15

1. Paired patch-clamp recordings were performed in cerebellar slices to study IPSCs evoked by interneurones (stellate and basket cells) in Purkinje cells. 2. IPSCs were first examined while keeping the presynaptic cell in the cell-attached mode. In some of these experiments IPSCs had a remarkably broad amplitude distribution. Large variabilities were associated with large mean IPSC amplitudes and were preferentially obtained with presynaptic basket cells. Action currents recorded from the presynaptic interneurone in the cell-attached mode were reproducible indicating that the variability occurs downstream of action potential generation. 3. The variability of IPSC amplitudes was observed independently of the instantaneous firing rate of the presynaptic cell, and could therefore not be ascribed to synaptic fatigue. 4. Highly variable IPSC amplitude were also obtained if the presynaptic interneurone was placed in whole-cell recording with a potassium-based intracellular solution. 5. If the recording pipette were filled with Cs+ ions a large increase in the mean of the IPSCs was observed within seconds after establishing the whole-cell recording. In Cs(+)-dialysed cells it was possible to modulate the mean IPSC amplitudes by altering the characteristics of the presynaptic stimulation. IPSC amplitudes obtained in response to presynaptic voltage pulses to 0 mV were large and had little scatter. IPSCs obtained in response to pulses near +60 mV, close to the reversal potential of presynaptic Ca2+ currents, had a much lower mean amplitude and also had little scatter. Thus presynaptic application of Cs+ ions both increases the mean amplitude and decreases the variability of the postsynaptic response. 6. To test whether interneurones could be coupled by electrical synapses, paired recordings were performed from neighbouring interneurones. No correlation was found between the firing patterns of such paired recordings, indicating that electrical coupling among presynaptic neurones is not responsible for large IPSC fluctuations as recorded in Purkinje cells. 7. Finally, IPSC fluctuations were investigated in paired recordings from two Purkinje cells. IPSCs corresponding to the activity of common interneurones were identified on the basis of temporal correlation. By plotting the amplitudes of such common IPSCs in one cell against those obtained simultaneously in the other cell, the pattern of IPSCs due to a single presynaptic neurone could be identified. These results show that fluctuations of IPSCs due to the same interneurone in one postsynaptic Purkinje cell are independent of those occurring in another Purkinje cell. 8. The results indicate that the major source of fluctuations is localized within the axonal arborization of presynaptic interneurones. The results with presynaptic Cs+ require that the fluctuations involve the concerted release of several presynaptic vesicles. Two possible mechanisms for such multiquantal events are discussed: fluctuations in presynaptic depolarization, and fluctuations in a regenerative Ca2+ amplification mechanism.
 ...
PMID:Fluctuations of inhibitory postsynaptic currents in Purkinje cells from rat cerebellar slices. 881 15

1. The recruitment order of 64 pairs of motor units, comprising 21 type-identified units, was studied during centrally evoked muscle contractions of the cat medial gastrocnemius (MG) muscle in an unanesthetized, high decerebrate preparation. Motor units were functionally isolated within the MG nerve by intra-axonal (or intramyelin) penetration with conventional glass microelectrodes. 2. Graded stimulation of the mesencephalic locomotor region (MLR) was used to evoke smoothly graded contractions, which under favorable conditions was estimated to reach 40% of maximum tetanic tension of the MG muscle. With this method of activation, 100% of slow twitch (type S) units, 95% of fast twitch, fatigue-resistant (type FR) units, 86% of fast twitch, fatigue-intermediate (type FI) units, and 49% of fast twitch, fatigable (type FF) units studied were recruited. 3. Motoneuron size as estimated by axonal conduction velocity (CV) was correlated with muscle-unit size as estimated by maximum tetanic tension (Po). Although the correlation between these properties was significant among type S and FR units, no significant correlation was found for these properties among type FI and FF units. 4. Motor-unit recruitment was ordered by physiological type (S > F, 100% of pairs; S > FR > FI > FF, 93% of pairs). Although none of the motor-unit properties studied predicted recruitment order perfectly, motor-unit recruitment was found to proceed by increasing Po (89% of pairs), decreasing contraction time (79% of pairs), decreasing fatigue index (80% of pairs), and increasing CV (76% of pairs). These percentages were significantly different from random (i.e., 50%). Statistically, all four motor-unit properties were equivalent in predicting recruitment order. These results are similar to those reported by other investigators for motor-unit recruitment order evoked from other supraspinal centers, as well as from peripheral sites. 5. When, however, motor-unit recruitment within pairs of motor units containing two fast-twitch (type F) units was examined, Po was a significantly better predictor of recruitment order than CV (85% vs. 52% of pairs). One explanation for this observation is that the correlation between Po and CV is high among type S, type FR units, and possibly among the lower-tension type FF units, but not among the remaining higher-tension type FF units. 6. The reproducibility of recruitment order in multiple contractions was investigated in 16 motor-unit pairs. Recruitment order was found to be variable in only three motor-unit pairs, all of which contained units of similar physiological type and recruitment threshold. 7. Analysis of recruitment order by pair-wise testing confirms the general conclusion reached in human studies that the muscle force level at recruitment for a motor unit is highly correlated with its strength. As an additional confirmation, the whole-muscle force level at recruitment for 41 units was measured in a series of contractions in which the rate of rise of muscle tension was limited to rates < 1,000 g/s. For these contractions, a significant correlation was found between muscle tension at recruitment and motor-unit Po.
 ...
PMID:Activation of type-identified motor units during centrally evoked contractions in the cat medial gastrocnemius muscle. I. Motor-unit recruitment. 882 39

To determine whether single motor units (MUs) in multitendoned muscles distribute tension to multiple tendons or instead focus tension selectively on a single tendon, we examined the distribution of tension generated by single MUs in the cat extensor digitorum lateralis (EDLat), and in its macaque homolog, the extensor digiti quarti et quinti (ED45). General properties of MUs (maximal tetanic tension, axonal conduction velocity, and twitch rise time) were similar in these muscles to those reported for other limb muscles in cats and monkeys. Most cat EDLat MUs were found to exert tension rather selectively on one of the three tendons of the muscle. Fast fatigable MUs were slightly but significantly more selective than fast fatigue-resistant and slow MUs. In contrast, and contrary to expectation, the macaque ED45 contained a lower proportion of MUs that exerted tension selectively on one of the two tendons of the muscle, and a higher proportion of relatively nonselective MUs. These findings suggest that the cat EDLat may consist of three functional subdivisions, each acting preferentially on a different tendon, whereas the macaque ED45 is more likely to function as a single multitendoned muscle.
 ...
PMID:Tension distribution of single motor units in multitendoned muscles: comparison of a homologous digit muscle in cats and monkeys. 903 Jun 32

In the presence of the monoamines serotonin and norepinephrine, spinal motoneurons can exhibit bistable behavior, in which a brief period of excitatory input evokes prolonged self-sustained firing. A brief inhibitory input returns the cell to the quiescent state. To determine whether motoneurons differ in their capacity for bistable behavior, intracellular recordings were obtained in the decerebrate cat preparation. To enhance the likelihood of encountering bistable behavior, the noradrenergic alpha1 agonist methoxamine was applied to the ventral surface of the cord. The capacity of the cells to produce bistable behavior was assessed from the duration of self-sustained firing evoked by a brief (1.5 s) excitatory synaptic input from muscle spindle Ia afferents. About 35% (17 of 49) of the cells produced steady self-sustained firing for >3 s and were considered fully bistable. The other 32 cells ( approximately 65%) were partially bistable, with self-sustained firing lasting <3 s. Fully bistable cells tended to have lower current thresholds for spike initiation and slower axonal conduction velocities than did partially bistable cells. This suggests that fully bistable motoneurons innervate fatigue resistant muscle fibers. The frequency-current (F-I) relations of the motoneurons were characterized with slow triangular current ramps. Fully bistable cells displayed an acceleration in firing rate immediately on initiation of rhythmic firing. The F-I gain after completion of the acceleration was positive. Fully bistable cells also displayed a hysteresis in the current level for firing threshold with the ascending threshold occurring at substantially higher current level than the descending one. Additionally, these current thresholds usually were centered about zero current, so that the ascending current threshold was positive while the descending current threshold was negative. This negative offset meant that fully bistable cells could exhibit tonic firing without depolarizing injected current. Partially bistable cells exhibited very different F-I characteristics. Firing rate acceleration was just as large as in fully bistable cells but did not occur until well above the current level needed to initiate rhythmic firing. F-I gain after acceleration was negative, there was little to no hysteresis between the ascending and descending firing thresholds, and both thresholds were above the zero current level. These properties of partially bistable cells suggest their functional role is in tasks requiring relatively brief, high forces. The low thresholds of fully bistable cells mean they will be readily recruited in low force tasks like posture, where their prolonged self-sustained firing would be advantageous.
 ...
PMID:Bistability in spinal motoneurons in vivo: systematic variations in rhythmic firing patterns. 970 51

Virtually all movements involve the recruitment of motor units from multiple muscles. Given the functional diversity of motor units (motoneurons and the muscle fibers they supply), the effective production of specific movements undoubtedly depends upon some principle(s) to organize the ensemble of active motor units. The principle acting to organize the recruitment of motor units within muscles is the size principle, whereby the first motor units to be recruited have the smallest values for axonal conduction velocity and contractile force, and are the slowest to contract and fatigue. Here we consider the possibility that the size principle applies in the recruitment of motor units across muscles, i.e., that regardless of their muscles of origin, active motor units are recruited in rank order, for example, from low to high conduction velocity. The benefits of orderly recruitment across muscles could be similar to the acknowledged advantages of orderly recruitment within muscles. One benefit is that the neural process involved in organizing active motor units would be simplified. In a muscle-based scheme, the size principle would organize only those motor units within individual muscles, leaving the nervous system with the additional task of coordinating the relative activities of motor units from different muscles. By contrast, in an ensemble-based scheme, orderly recruitment of all motor units according to the size principle would automatically coordinate motor units both within and across motor nuclei. Another potential benefit is the provision for movements with smooth trajectory, the result of interleaving the divergent torque contributions made by motor units from muscles that differ in their orientations about joints. Otherwise, if order were restricted within muscles, the torque trajectory of a joint would change unevenly as participating muscles begin contracting at different times and grade activity at different rates. These considerations support speculation that motor units recruited from co-contracting muscles are collectively recruited according to the size principle.
 ...
PMID:Orderly recruitment among motoneurons supplying different muscles. 1008 11

Contractile properties and conduction velocity were studied in 202 single motor units of intact rat triceps surae muscles activated by intra-axonal (or intra-myelin) current injection in L5 or L6 ventral root to assess the factors that determine the expression of sag (i.e., decline in force after initial increase during unfused tetanic stimulation). Sag was consistently detected in motor units with unpotentiated twitch contraction times <20 ms. However, the range of frequencies at which sag was expressed varied among motor units such that there was no single interstimulus interval (ISI), with or without adjusting for twitch contraction time, at which sag could be detected reliably. Further analysis indicated that using the absence of sag as a criterion for identifying slow-twitch motor units requires testing with tetani at several different ISIs. In motor units with sag, the shape of the force profile varied with tetanic frequency and contractile properties. Simple sag force profiles (single maximum reached late in the tetanus followed by monotonic decay) tended to occur at shorter ISIs and were observed more frequently in fatigue-resistant motor units with long half-relaxation times and small twitch amplitudes. Complex sag profiles reached an initial maximum early in the tetanus, tended to occur at longer ISIs, and were more common in fatigue-sensitive motor units with long half-relaxation times and large twitch amplitudes. The differences in frequency dependence and force maximum location suggested that these phenomena represented discrete entities. Successive stimuli elicited near-linear increments in force during tetani in motor units that never exhibited sag. In motor units with at least one tetanus displaying sag, tetanic stimulation elicited large initial force increments followed by rapidly decreasing force increments. That the latter force envelope pattern occurred in these units even in tetani without sag suggested that the factors responsible for sag were expressed in the absence of overt sag. The time-to-peak force (TTP) of the individual contractions during a tetanus decreased in tetani with sag. Differences in the pattern of TTP change during a tetanus were consistent with the differences in force maximum location between tetani exhibiting simple and complex sag. Tetani from motor units that never exhibited sag did not display a net decrease in TTP during successive contractions. These data were consistent with the initial force decrement of sag resulting from a transient reduction in the duration of the contractile state.
 ...
PMID:Sag during unfused tetanic contractions in rat triceps surae motor units. 1036 85

Patients with multifocal motor neuropathy may complain of muscle fatigue, even though the degree of conduction block assessed at rest has improved with treatment. To explore the mechanism involved, we examined changes in muscle force during maximum voluntary contraction (MVC) and monitored conduction block before and after MVC in five patients with multifocal motor neuropathy. The results were compared with those for the contralateral unaffected homonymous muscles. For one patient, who had bilateral involvement, a normal subject of a similar age and stature served as the control. Results of conduction studies were also compared with those from six patients with amyotrophic lateral sclerosis (ALS) with similar compound muscle action potential (CMAP) amplitudes after proximal stimulation. During MVC for 60 s, the affected muscles developed prominent fatigue; the force at the end of contraction compared with the initial force was significantly lower for the affected muscles [42 +/- 19% (mean +/- standard deviation) of the initial force] than for the control muscles (94 +/- 9%; P = 0.01). After MVC, the amplitude ratio of CMAPs after proximal versus distal nerve stimulation transiently decreased to 19 +/- 14% of that before MVC in the affected muscles, but not in the control muscles (94 +/- 3.8% of that before MVC) and in patients with ALS (95 +/- 6.7%). In one patient with a focal lesion in the forearm, nerve excitability was monitored at the lesion site before and after MVC for 120 s. There were significant increases in axonal threshold (approximately 48%) and supernormality (approximately 135%) immediately after MVC, suggesting that the axonal membrane had undergone hyperpolarization and, by extrapolation, that this had precipitated the conduction block. This study is the first to show that activity-dependent conduction block plays a role in human disease by causing muscle fatigue.
 ...
PMID:Activity-dependent conduction block in multifocal motor neuropathy. 1090 90

Functionally useful reanimation of paralyzed limbs generally requires reliable, finely graded control of muscle recruitment and force with minimal fatigue. We used force and electromyographic (EMG) recordings in combination with myofibrillar adenosine triphosphatase activity and glycogen depletion analysis to investigate the recruitment properties of intramuscular (IM) and nerve cuff (NC) stimulating electrodes implanted acutely or chronically in cat hindlimbs. Overall, 32 muscles were submaximally stimulated with current intensities producing approximately 20% of maximal twitch force using 330 ms trains of pulses at 20 and 40 pps. Both the glycogen-depletion and fatigue-test results were found to be difficult to interpret because NC stimulation resulted in surprisingly unstable recruitment during such trains. Fluctuations of force and M-waves within trains of identical stimuli were significantly greater for NC than for IM stimulation. NC stimulation produced much steeper recruitment curves and a reduced tetanus/twitch ratio compared to IM stimulation. IM stimulation produced more reliable and less fatigable recruitment of a mix of motor unit types that tended to be localized in neuromuscular compartments containing, or adjacent to, the IM electrode. We hypothesize that trains of submaximal stimulation applied through NC electrodes resulted in fluctuating recruitment because this electrode configuration magnifies the effects of refractoriness and small changes in axonal excitability during pulse trains.
 ...
PMID:Recruitment properties of intramuscular and nerve-trunk stimulating electrodes. 1100 7


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>