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Biomedical subjects

J Borg

Publications and source records attributed to J Borg.

At least 91 records · Page 5Linked to original sources

The fatigue of voluntary contraction and the peripheral electrical propagation of single motor units in man.

1. Single human motor units from the short extensors of the toes were classified by their voluntary threshold and axonal conduction velocity. The voluntary discharge intervals, and the shortest discharge intervals at which action potentials were conducted to the muscle fibres, were studied during maximal voluntary effort maintained for 1 min, and were compared with the intervals calculated to be necessary for full fusion.2. Electromyographic techniques were used. High selectivity of the recordings was obtained after blocking of the main motor nerve with lidocaine in subjects with an accessory innervation of just a few motor units or 6 months after lesions to intramuscular nerve twigs, when the muscle-fibre density within the motor units was increased.3. For a whole minute of maximal voluntary effort, motor units with low threshold and low conduction velocity fired tonically at a rate that should have been sufficient for maximal tension. These intervals were longer than the intervals at which blocking occurred.4. In ordinarily motivated and untrained subjects, motor units with high threshold and high conduction velocity fired tonically at intervals sufficient for full tension for some seconds. Under these circumstances the voluntary intervals were longer than the critical ones.5. Through extraordinary motivation and training, motor units with high threshold and high conduction velocity could also be driven tonically for 20-60 s at the high rates required for full tension. The critical intervals then approached the voluntary ones. Blockings occurred and increased in frequency as the contraction continued.6. When motor units with high threshold and high conduction velocity were tetanized electrically at 20 Hz, which was the lowest discharge rate of these units in tonic voluntary contraction, blockings occurred within 60 s.7. The role of the peripheral block is discussed in relation to loss of tension in prolonged voluntary contraction.

Action Potentials↗

Effects of prior activity on the conduction in single motor units in man.

The slowing of the conduction of an impulse travelling in the relative refractory period of a prior impulse was studied in single short toe extensor motor units in man. Paired electrical stimuli were delivered to the peroneal nerve and single motor unit recordings were achieved by special electromyographic techniques. The delay of the second impulse, propagated during the relative refractory period of the prior impulse, limited the unit discharge, frequency. The shortest motor unit response interval ranged from 3 to 5 ms and was inversely related to the axonal conduction velocity. The delay of the second impulse in the proximal nerve segment was most pronounced close to the stimulus point but continued during propagation for several milliseconds. Further delay occurred distally. The slowing of the conduction of the second impulse after delivering paired electrical nerve stimuli offers a new parameter in single motor unit studies and also makes it possible to measure the axonal refractory period after electrical nerve excitation without using blocking nerve impulses.

Adult↗

Glutamine and glutamate transport in cultured neuronal and glial cells.

The uptake of L-glutamine in neuronal and glial cultures derived from rat cerebral hemispheres was found to be mediated by a low affinity-high capacity mechanism which was concentrative in both cell types; the calculated Km and Vmax were twice as high in glial than in neuronal cultures. In contrast L-glutamate was taken up by a high affinity system which was particularly efficient and concentrative in the glial cells. Different transport mechanisms for L-glutamine appeared to operate in the two cell types: L-glutamine uptake in neurons was sodium-dependent, specifically inhibited by L-glutamine but not affected by high potassium concentrations in the external medium; on the other hand, glial glutamine transport was decreased when potassium concentration increased, was sodium-independent and significantly inhibited by 3 structurally related amino acids. No significant contribution of homoexchange could be detected in either cell type. After [14C]glutamine preincubation, the radioactivity released into the superfusion medium by neuronal cells was increased in the presence of a high potassium concentration; no such effect could be seen in the case of glial cultures. A regulatory mechanism is suggested where astrocyte depolarization and repolarization would channel a flux of glutamine toward the neurons, subsequent to a glutamate flux in the opposite direction.

Animals↗

Neurotransmitter modifications in human cerebrospinal fluid and serum during hepatic encephalopathy.

The concentrations of catecholamines, serotonin, histamine and GABA as well as some of their precursors and metabolites were measured in the CSF and the serum of human patients at different grades of hepatic encephalopathy. In all grades the CSF concentrations of the neurotransmitters were much increased over control levels, while the amount of metabolites varied with the grade of coma. The data suggest modifications of the cerebral turnover of dopamine, norepinephrine and serotonin. The "false transmitters" also occurred in high concentration in all grades of hepatic coma and could play a role in the alterations of synaptic transmission. The present results suggest that the biochemical changes between grade 2 and grade 4 hepatic coma could be due to an inhibition of dopamine beta-hydroxylase. Moreover, the levels of neurotransmitter precursors, tyrosine and 5-hydroxytryptophan, showed enhancement in grades 2 and 3 followed by an important reduction in grade 4. Finally, it seems that the biogenic amines measured in the CSF are of central origin and that their quantification in human lumbar fluid gives new information on the central mechanisms involved in hepatic encephalopathy.

5-Hydroxytryptophan↗

Firing properties of single human motor units on maintained maximal voluntary effort.

The discharge properties on maintained maximal voluntary effort, axonal conduction velocity (a.c.v.) and contraction time (c.t.) of single human motor units were studied. Electromyographic (EMG) techniques were used and sufficient selectivity was obtained after repeated lesions to the terminal nerve twigs and consequent collateral sprouting, or by blocking the main muscle nerve in subjects with an accessory nerve supplying just one or a few units, or using high impedance wire electrodes. Most units with a.c.v. above 45 m/s and c.t. below 50 ms had maximal voluntary firing rates of about 50 Hz. On prolonged maximal effort, however, their rates rapidly decreased and after some seconds to a minute they ceased to respond tonically. As long as their motoneurons fired their EMG potentials were mainly intact and their twitch tension was significant. Most units with a.c.v. below 40 m/s and c.t. above 60 ms fired initially at 30 Hz, decreased slowly in firing rate and continued at 20 Hz for some minutes. We conclude that there is a central fatigue of units with short c.t. and high a.c.v. which protects their peripheral regions from severe exhaustion, but that there is no significant central fatigue of units with long c.t. and low a.c.v. We emphasize, however, that most units are intermediate in their properties.

Action Potentials↗

Axonal refractory period of single short toe extensor motor units in neuropathies and neuromuscular diseases.

Electromyographic recordings were carried out on 36 patients with neuropathies and neuromuscular disorders with a selectivity permitting identification of single motor unit potentials during maximal voluntary effort and after supramaximal nerve stimulation. The axonal conduction velocity and refractory period of 117 motor units were determined and the findings were compared to those in previously studied normal subjects. The axonal conduction velocity spectrum was 15-52 m/s. Fifteen per cent of all motor units had axonal conduction velocities below 30 m/s which is below the normal range. When test stimulus strength was 10% above the axonal threshold at rest the refractory period was 1.88 +/- 0.43 ms which is slightly longer than the corresponding value in healthy subjects (1.67 +/- 0.25 ms). The relationship between the axonal conduction velocity and refractory period observed in healthy subjects did not hold for these patients. Thirty-eight per cent of all motor motor units with axonal conduction velocities within the normal range had refractory periods longer than 2.0 ms which was only infrequently observed in healthy subjects. When test stimulus strength was 50% above the axonal threshold at rest the refractory period was 1.16 +/- 0.42 ms which was significantly longer (p less than 0.02) than in healthy subjects (0.64 +/- 0.21 ms). At this stimulus strength 40% of all motor units with axonal conduction velocities within the normal range had refractory periods above 1.0 ms which was never the case in healthy subjects. The significance of these findings with regard to the clinical application of the Hopf technique for determining the conduction velocity spectrum of peripheral motor nerves is discussed.

Adult↗

Axonal refractory period of single short toe extensor motor units in man.

The aim of this study was to test the reliability of the commonly used blocking technique for measuring the conduction velocity spectrum of the peripheral motor nerve in man, as first described by Hopf in 1962. Electromyographic recordings were carried out with a selectivity permitting identification of single motor unit potentials. The conduction velocity of the single alpha motor axon was determined by a direct technique and by the blocking technique. the refractory period was determined by comparison of the results of these two techniques. The refractory period was studied in relation to the strength of the testing stimulus, axonal conduction velocity, skin temperature and age of the subject. When the strength of the test stimulus increased from 10% to 50% above the axonal threshold, the refractory period decreased from 1.7 to 0.6 ms. An inverse relationship between the axonal conduction velocity and the refractory period was observed. When skin temperature was 4 degrees C subnormal the refractory period was significantly prolonged; at 10 degrees C subnormal it was more than doubled. The same relationship between axonal conduction velocity and the refractory period was observed in both young and elderly subjects. The significance of these findings for the clinical application of the blocking technique is discussed.

Adult↗

Effect of cyclic nucleotides on high affinity uptake of L-glutamate and taurine in glial and neuroblastoma cells.

Cultured glial cells (clones NN and I6) and neuroblastoma cells (clones M1 and M1NN) were used to study the effect of cyclic nucleotides on high affinity uptake of L-glutamate and taurine. Treatment of NN cells with a mixture of dBcAMP and BrcGMP for one or two days resulted in a more than 3-fold increase in the Vmax of L-glutamate high affinity uptake. Similar but smaller change was observed in a related glial clone (I6). Effects of cyclic nucleotide derivatives on high affinity uptake of L-glutamate by neuroblastoma cells (clones M1 and M1NN) or of taurine by both glial or neuroblastoma cells were either smaller or absent. Some differences were found in kinetic parameters of uptake of L-glutamate and taurine by original and re-isolated cellls, respectively. It is possible that these differences resulted from co-cultivation of glial and neuronal cells. However, since some values reported in this paper differ to some extent from those published previously, some other factors, such as subcloning, may have been responsible.

Animals↗

Effects of amino acids on calcium uptake by glial and neuroblastoma cells.

The uptake of [45Ca] has been studied in clonal glial and neuronal cells. It was somewhat more efficient in the neuroblastoma clone M1 compared to glial clones. In all cases [45Ca] uptake was shown to depend on the phosphate concentration in the incubation medium. It was decreased by the ionophore A 23187 at 200 microM concentration in both neuronal and glial clones. The influence of amino acids some of which are putative neurotransmitters was investigated; the interactions between [45Ca] uptake and these amino acids were related to their concentration and the type of cells used (neuronal or glial). L-aspartate and taurine for example had two opposite effects on [45Ca] uptake by the glial clone NN at two different concentrations; they could therefore play a role in the control of calcium level in the synaptic cleft.

Amino Acids↗

High-affinity uptake of gamma-aminobutyric acid in cultured glial and neuronal cells.

Both glial and neuronal cells maintained in primary culture were found to accumulate [3H]GABA by an efficient "high-affinity" uptake system (apparent Km = 9 muM, Vmax = 0.018 and 0.584 nmol/mg/min, respectively) which required sodium ions and was inhibited by 1 mM ouabain. Strychnine and parachloromercuriphenylsulfonate (pCS) (both at 1mM) also strongly inhibited uptake of [3H]GABA, but metabolic inhibitors (2,4-dinitrophenol, potassium cyanide, and malonate) were without effect. Only three structural analogs of GABA (nipecotate, beta-alanine, and 2,4-diaminobutyrate) inhibited uptake of [3H]GABA, while several other compounds with structural similarities to GABA (e.g. glycine, L-proline, and taurine) did not interact with the system. The kinetic studies indicated presence of a second uptake (Km = 92 muM, Vmax = 0.124 nmol/mg/min) in the primary cultures containing predominantly glioblasts. On the other hand, only one of the neuronal cell lines transformed by simian virus SV40 appeared to accumulate [3H]GABA against a concentration gradient. Apparent Km of this uptake was relatively high (819 muM), and it was only weakly inhibited by 1 mM ouabain and 1 mM pCS. The structural specificity also differed from that of the uptake observed in the primary cultures. Significantly, non of the nontransformed continuous cell lines of either tumoral (glioma, C6; neuroblastoma, M1; M1NN) or normal (NN;I6) origin actively accumulated [3H]GABA. It is suggested that for the neurochemical studies related to GABA and requiring homogeneous cell populations, the primary cultures offer a better experimental model than the continuous cell lines.

4-Chloromercuribenzenesulfonate↗

Axonal conduction velocity and voluntary discharge properties of individual short toe extensor motor units in man.

1. The axonal conduction velocity and the voluntary discharge properties of 120 short toe extensor motor units were studied in man. 2. Electromyographic techniques were used which permitted the identification of individual motor unit potentials after proximal and distal electrical nerve stimulation and during maximum voluntary effort. 3. The necessary selectivity of the e.m.g. recordings was achieved in two circumstances. In some subjects, previous motor nerve lesions distal to the point of stimulation had led to collateral sprouting with larger motor unit potentials. In other subjects an accessory deep peroneal nerve was present, so that lidocaine block of the main motor nerve left a small number of innervated motor units. 4. The axonal conduction velocities of the individual motor units ranged from 30 to 54 m/sec with most motor units between 35 and 45 m/sec. 5. Motor units which voluntarily could be driven continuously at frequencies below 10/sec had axonal conduction velocities between 30 and 45 m/sec. 6. Motor units which on voluntary drive responded only in high frequency bursts had axonal conduction velocities between 40 and 54 m/sec. 7. Motor units with intermediate voluntary discharge properties had intermediate axonal conduction velocities. 8. Thus a relationship was established between voluntary discharge properties and axonal conduction velocity.

Action Potentials↗