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At least 19 recordsLinked to original sources
PubMed1979

Comparison of pre-junctional alpha-adrenoceptors at the neuromuscular junction with vascular post-junctional alpha-receptors in cat skeletal muscle.

1 Activation of pre-junctional alpha-adrenoceptors at the skeletal neuromuscular junction enhances acetylcholine release whereas activation of such receptors at autonomic nerve endings inhibits transmitter output. In the present study the characteristics of pre-junctional alpha-adrenoceptors at motor nerve terminals have been compared with post-junctional (vascular) alpha-adrenoceptors in the cat hind limb.2 Reversal of partial (+)-tubocurarine blockade of contractions of the tibialis anterior muscle was used to monitor pre-junctional activity and increases in hindlimb vascular resistance to assess post-junctional actions at alpha-adrenoceptors.3 Responses to intra-arterial injections of noradrenaline, adrenaline, phenylephrine, oxymetazoline, methoxamine and clonidine were monitored. Dose-response lines for all the compounds except clonidine were parallel. The latter agent produced only weak and inconsistent effects.4 Ratios of the doses of the agents required to produce pre- and post-junctional effects indicated that oxymetazoline and adrenaline possessed some preferential activity at post-junctional sites, whereas the remaining agents were non-selective in their actions. If dose-ratios with respect to noradrenaline were compared at the two sites none of the compounds possessed a marked degree of selectivity.5 In the presence of phentolamine or tolazoline, dose-response curves to the pre- and post-junctional effects of phenylephrine were shifted to a similar extent. Thymoxamine showed preferential activity as a pre-junctional alpha-receptor antagonist.6 In comparing the results of this study with those of other authors, it is apparent that there are marked differences in the characteristics of pre-junctional alpha-receptors at the skeletal neuromuscular junction and at autonomic nerve endings. The pre- and post-junctional alpha-receptors in skeletal muscle show less divergence.

Animals↗
PubMed1978

An analysis of the dose-response relationship at voltage-clamped frog neuromuscular junctions.

1. Frog neuromuscular junctions were viewed with Nomarski optics and voltage clamped. Agonist was applied ionophoretically and agonist concentrations were measured using a micro-electrode sensitive to quaternary amines. 2. The dose-response relationship was studied using the agonists carbamylcholine, suberyldicholine and hydroxyphenyl-propyltrimethylammonium. 3. With all of these agonists, it appeared that the ACh receptor could be active when either one or two agonist binding sites were occupied. The receptor was much more likely to be active when both sites were occupied. Agonist dissociation constants and receptor activation probabilities were estimated by non-linear regression techniques for several possible receptor activation schemes.

Animals↗
PubMed1975

Estimates of statistical release parameters from crayfish and frog neuromuscular junctions.

1. Transmitter release at crayfish and frog neuromuscular junctions was studied by recording synaptic potentials with extracellular or intracellular glass micro-electrodes. 2. The binomial release parameters n and p were calculated using the experimental observations for the mean number of quanta (m) released in a series of trials, the variance (var) of the quantum content distribution and the number of transmission failures (n-o). 3. In one series of experiments on frog neuromuscular junction, action potentials were blocked by tetrodotoxin. Transmitter release was limited to a circumscribed part of the nerve terminal by focal stimulation with a glass micro-electrode. Values for m were between 0-6 and 5-7 and calculated values for n ranged from 3 to 23. p was between 0-05 and 0-48. In a second series of experiments on frog neuromuscular junction transmitter release was evoked by conventional stimulation of the nerve trunk in Mg-Ringer. m was mostly between 20 and 60 and in the same experiments n was calculated to be between 70 and 125. Values for p ranged from 0-25 to 0-48. 4. It can be concluded from the present results that transmitter release at frog neuromuscular junction is described by binomial statistics as is the case for neuromuscular junction of crayfish. 5. In comparing the values for n for the two series of experiments on frog neuromuscular junction it appears that n is dependent on the length of the activated synaptic contact. The numbers for n calculated from frog neuromuscular junction are of the same order of magnitude as the number of 'active zones' seen in the corresponding length of the synaptic nerve terminal.

Action Potentials↗
PubMed1975

The effects of diethyl ether, enflurane, and isoflurane at the neuromuscular junction.

The actions of diethyl ether, enflurane, and isoflurane at the neuromuscular junction were examined in isolated guinea pig lumbrical muscles. These anesthetics depressed the ability of carbachol to depolarize the endplate region; this depression of depolarization did not show competitive kinetics. None of the anesthetics altered the affinity of the acetylcholine receptor for d-tubocurarine, i.e., the dissociation constant of d-tubocurarine was unchanged. Since diethyl ether, enflurane, and isoflurane produced no observable alteration of the receptor, the antagonism of the drug-induced depolarization of the neuromuscular junction appears to be exerted at a stage subsequent to reaction with the receptor. (Key words: Anesthetics, volatile, diethyl ethers; Anesthetics, volatile, euflurane; Anesthetics, volatile, isoflurane; Neuromuscular relaxants, d-tubocurarine; Neuromuscular junction.).

Acetylcholine↗
PubMed1979

Frequency sweep analysis of neuromuscular junction continuity.

A new technique for measuring neuromuscular junction continuity is described. Junctional transmission is evaluated by integration of the electromyographic (EMG) response induced by intramuscular electrical stimulation. The unique characteristics of this monitoring technique are the use of intramuscular stimulation and a varying stimulation rate. The stimulus frequency is made to increase exponentially from 1 to 100 pulses per second over a period of 10 or 15 seconds. Thin coiled wire electrodes are used for stimulation and recording of the EMG response. The frequency sweep electromyogram (FS-EMB) response was measured in uncurarized and curarized tibialis anterior muscle of cat. In the uncurarized preparation, the FS-EMG response was only slightly decreased with an increasing stimulus frequency. During neuromuscular blockade with d-tubocurarine the FS-EMG response diminished with increasing frequency. The response failed at successively lower frequencies during deeper levels of neuromuscular block. Recovery proceeded in the reverse order. The frequency sweep technique provides quantitative assessment of neuromuscular junction continuity over a broad spectrum of driving frequencies without inducing fatigue. This method does not require force measurements nor voluntary effort. Intramuscular stimulation minimises painful stimuli thus making the frequency sweep technique suitable for evaluating neuromuscular transmission in either conscious or unconscious individuals.

Action Potentials↗
PubMedDate not supplied

Pathology of the neuromuscular junction.

Diagnosis of neuromuscular disease by the study of motor endplate structure in the light and electron microscopes is probably one of the most specialized examinations in the field of neuropathology. The classical means of staining endplates using gold, silver or methylene blue are described as well as more modern techniques suitable for light microscopy. Specific abnormalities in patterns of terminal innervation after methylene blue staining are noted. Techniques for localizing endplates suitable for electron microscopic study are given and some of the typical changes that occur in endplate structure in some neuromuscular diseases are indicated.

Biopsy↗
PubMed1979

Glutamate potential : differences from the excitatory junctional potential revealed by diltiazem and concanavalin A in crayfish neuromuscular junction.

1. The effect of diltiazem and concanavalin A (Con A) on the crayfish neuromuscular junction was investigated in order to compare the action of L-glutamate with that of the excitatory transmitter. 2. When diltiazem (0.3 nM) was added to the perfusion fluid, the iontophoretic glutamate potential was reduced to about half, whereas the amplitude of excitatory junctional potentials (EJPs) increased by about two times. 3. Dose-response curves of L-glutamate suggested that diltiazem acted in a non-competitive manner. The decrease in amplitude of the glutamate potential caused by diltiazem was not due to the acceleration of desensitization of the glutamate receptor. 4. The increase in amplitude of EJPs caused by diltiazem was due to the increase in membrane resistance. The quantal content and size of extracellular EJPs were not affected by diltiazem. 5. In normal saline, bath application of glutamate decreased the amplitude of both glutamate potentials and EJPs because of desensitization of the glutamate receptor. The decrease in amplitude of the glutamate potential was completely prevented by previous application of Con A (10(-6) M). On the other hand, Con A had no influence on the decrease in amplitude of EJPs. 6. Some possible explanations of these pharmacological differences between glutamate potentials and EJPs revealed by diltiazem and Con A are considered.

Animals↗
PubMed1977

Transmitter mobilization at the frog neuromuscular junction.

During frequency facilitation of frog neuromuscular junctions depressed by Mg++, the relationship between quantal content (m) and frequency of stimulation (0.5 to 8 Hz) is exponential. The slope of the relationship (k) reflects transmitter mobilization and the zero-frequency intercept (mo) reflects the basic release process. The catecholamines, tetraethylammonium, guanidine and raised [Ca++]o increased mo but had no effect on k. At junctions where release ranged from 200 to 500 quanta sec-1 during steady-state conditions, this result was interpreted to mean that the drugs increased both transmitter release and mobilization. An analog of hemicholinium-3, DMAE, depressed k, reflecting the ability of DMAE to depress transmitter mobilization. The alternative possibility that the frequency facilitation relationship was altered by effects of the drugs on the number of activated release sites was also considered.

Animals↗
PubMed1975

An ultrastructural and cytochemical study of neuromuscular junctions in echinoderms.

The ultrastructure of neuromuscular junctions in various organs of a starfish and a holothurian was studied. All neurons were found to contain large (100-250 nm), dense-core vesicles. Cytochemical tests for acetylcholinesterase were negative for these neurons. The presence of proteinaceous neurosecretory material was contested by enzymatic digestion (pepsin) which did not attack the dense-core vesicles, as well as by incubation in phosphotungstic acid (PTA) which did not stain these structures. Staining with dichromate produced a positive reaction for 5-hydroxytryptamine. In the absence of synaptic modifications even after specific staining with PTA, the transmission of nervous impulses is effectuated through exocytosis of 5-hydroxytryptamine at nerve endings in the muscle tissue.

Acetylcholinesterase↗
PubMed1976

Non-uniform probabilities of quantal release at the crayfish neuromuscular junction.

1. Transmitter release at the neuromuscular junction of the crayfish walking leg has been found to deviate from binomial predictions immediately after the onset of repetitive stimulation of the presynaptic nerve at frequencies of at least 15 Hz. 2. After several minutes of continuous stimulation, and at lower rates of stimulation, however, the number of quanta released could be described quite well by binomial or Poisson statistics. 3. Deviations from the theoretical expectations were characterized by (a) fewer release failures than predicted, (b) occasions in which the number of quanta released was more than the estimated number of quanta available for release, and (c) a tendency for the data to be underdispersed. 4. Each of these three characteristics are consistent with the hypothesis that different releasable quanta may have different probabilities of responding to a nerve impulse. 5. Using two different methods, different values of the non-uniform probabilities were estimated from the data. At each synaptic site at least one of the estimated probabilities was very high. 6. The need for caution in interpreting statistical description of quantal release is emphasized.

Animals↗
PubMed1978

Determination of dose-response curves by quantitative ionophoresis at the frog neuromuscular junction.

1. Quantitative ionophoresis at the neuromuscular junction is possible when (a) the drug is released from appropriate distances (15--20 micrometer for most drugs), (b) the topology of receptors is known and (c) high resistance drug pipettes (100--200 M omega) are sued. 2. With this method, drug concentration-endplate conductance relations were determined in voltage-clamped end-plates of the frog for the agonists ACh, carbamylcholine (CCh) and suberyldicholine (SubCh). 3. Based on the co-operative and independent model, theoretical dose-response curves were computed using as parameters the Hill coefficient nH, maximum conductance gmax., and apparent dissociation constant K. It was found that the co-operative model fitted the data much better than the independent model. 4. Based on the co-operative model, the mean maximum conductance for ACh was gmax. = 169 nS/micrometer, equivalent to 9000 ionic channels/micrometer length of a nerve terminal which can be opened at high drug concentrations. 5. The maximum conductance for CCh at--80 mV membrane potential was, on the average, 78% of that for ACh measured at the same end-plates. This value is termed the relative efficacy of CCh. 6. The mean values for the apparent dissociation constant K were 27.8 micrometer for ACh, 336 micrometer for CCh and 18 micrometer for SubCh. 7. The inhibition of the acetylcholinesterase activity by edrophonium (3--10 micrometer) affected only the local ACh concentration at the receptor sites, but not gmax. and nH. 8. Dose-response curves measured before and after removal of single nerve terminals in collagenase-treated muscle fibres showed no change in the nH, gmax. and K. A slight increase in gmax. to a value of 218 nS/micrometer observed comparing collagenase-treated and untreated end-plate. 9. Desensitization of receptors may occur in the range of several tens of milli-seconds.

Acetylcholine↗
PubMed1977

Action of brown widow spider venom and botulinum toxin on the frog neuromuscular junction examined with the freeze-fracture technique.

1. Structural changes which normally accompany transmitter release at frog neuromuscular junctions are visualized with the freeze-fracture technique. The effects of brown widow spider venom and botulinum toxin were evaluated in terms of their ability to block or produce these structural changes. Changes produced by these neuropoisons were correlated with their known effects on neurotransmitter release. 3. Fusion of synaptic vesicles with the presynaptic plasmalemma, normally evoked by electrical stimulation, was abolished at neuromuscular junctions from frogs treated with botulinum toxin. 3. The concentration of large intramembranous particles in the presynaptic plasmalemma, an indication of the excess of synaptic vesicle fusion over recovery of synaptic vesicle membrane, was increased by treatment with brown widow spider venom, even in the presence of botulinum toxin. 4. When external calcium was present, sites of vesicle fusion induced by brown widow spider venom, as well as by electrical stimulation, were located mainly in the active zone. In the absence of external calcium, many plasmalemmal deformations, also though to be sites of vesicle fusion, were more evenly dispersed over the presynaptic surface of nerve terminals. 5. Botulinum toxin decreased the number of vesicle fusion sites in the active zone induced by spider venom in the presence of external calcium but had little effect on the number of fusion sites induced by spider venom in the absence of external calcium. 6. Nerve terminals soaked in a sodium-free Ringer solution were partially depleted of vesicles. Addition of spider venom to this Ringer did not cause additional depletion of vesicles. 7. Formation of cation-permeable channels in the presynaptic membrane could account for these effects of spider venom on the frog neuromuscular junction. Botulinum toxin blocks vesicle fusion by some means which is not yet understood.

Animals↗
PubMed1976

L-glutamate as an excitatory transmitter at the Drosophila larval neuromuscular junction.

The possibility that L-glutamate is the excitatory transmitter at the Drosophila larval neuromuscular junction and the ionic basis of its action on the muscle membrane are examined. 2. Iontophoretically applied L-glutamate causes muscle depolarization (L-glutamate potential) if and only if the L-glutamate pipette is within a few mum of the nerve ending. D-glutamate, substance P, ACh and GABA are ineffective. 3. Bath-applied L-glutamate produces similar changes in the time course and amplitude of miniature excitatory junctional potential (m.e.j.p.), excitatory junctional potential (e.j.p.) and the L-glutamate potential. 4. Neuromuscular transmission and excitation-contraction coupling are operative in a haemolymph-like solution containing 1 mM L-glutamate. 5. The reversal potentials of the e.j.p. and the L-glutamate potential are identical to each other, changing similarly with changes in the ionic compositions of the external medium (twelve solutions). 6. The ionic dependence of the reversal potentials is predicted from an extended constant-field equation using a ratio of sodium:potassium permeabilities of PNa/PK=1-3, and a ratio of magnesium:potassium permeabilities of PMg/PK=4-7. 7. It is concluded that L-glutamate is, or is an agonist of, the excitatory transmitter at certain Drosophila larval neuromuscular junctions.

Acetylcholine↗
PubMed1978

Genetic dissection of short-term and long-term facilitation at the Drosophila neuromuscular junction.

Transmitter release at the Drosophila larval neuromuscular junction may be increased by previous activity of the nerve. This facilitation phenomenon involves at least two processes, one short-term and other long-term. These are shown to based on different mechanisms because (i) a mutant was found that had abnormal long-term facilitation but normal short-term facilitation; and (ii) long-term facilitation was eliminated by tetrodotoxin or by removing external Na+ but short-term facilitation was not. In long-term facilitation, there was a prolonged release of transmitter due to a prolonged Ca2+ sensitivity of the presynaptic terminal after each nerve stimulus. The cause of this is probably accumulation of Na+ inside the nerve terminal.

Animals↗
PubMed1978

[Formation of the neuromuscular junction in cultures of rat embryonic cells].

The morphological evidence of the primary nerve muscle contacts are described. They consist of areas of cholinesterase activity (detected histochemically) localized on the myotube membranes and of mutiple clusters of ACh receptors whose 125I-alpha-bungarotoxin binding sites are revealed by radio-autography. After the stage of the primary nerve muscle contacts, some of which seem transient, characteristic neuromuscular junctions appear. These neuromuscular junctions which possess subneural infoldings are similar to the end-plates of the Rat in vivo.

Animals↗
PubMed1977

Time course and magnitude of effects of changes in tonicity on acetylcholine release at frog neuromuscular junction.

1. The time course for the changes in miniature end-plate potential (min epp) frequency and in epp amplitude produced by alterations in the tonicity of the Ringer at the frog neuromuscular junction was studied. The relations between the tonicity and min epp frequency as well as epp amplitude were also investigated. 2. The change in min epp frequency occurred within 1 min after the start of the change in the tonicity of the extracellular solution. Following a shift to a hypertonic solution, the min epp frequencies were often maintained at a relatively steady, elevated level, even with large (+100 mosM) changes in tonicity. In other instances the elevation was transitory like the reported data for the rat neuromuscular junction. Essentially the same results were obtained in very low Ca2+-Ringer. Unlike the rat neuromuscular junction, the final level after hours of the increased min epp frequency caused by raising the osmolarity by more than 75 mosM was well above the control level. Following the return from a hypertonic to an initial solution there was a prompt decrease in min epp frequency to about the initial level; there was no indication of the transitory depression in min epp frequency following the return from hypertonic solution that has been reported in mammals. 3. Until the osmolarity of the Ringer reached about 420 mosM, the frequency of min epp continued to rise along a line relating log (min epp frequency) to (osmolarity)0.5. When the osmolarity exceeded 460 mosM, the relation started to level off. 4. The hypothesis that the min epp frequency in a Ringer with a given increased tonicity is a fixed multiple of the frequency in normal Ringer is not in accord with the data. 5. The decrease in epp amplitude caused by markedly hypertonic solutions also came about within 1 or 2 min after the start of the change in the tonicity of the solution surrounding the nerve terminal. 6. Hypertonic solutions did not appear to affect facilitation. 7. Below 360 mosM increasing the tonicity of the Ringer had little effect on the amplitude of epp. Above this level the amplitude decreased as the tonicity increased. At a given junction an increase in tonicity in a range above 360 mosM can cause an increase in min epp frequency and a decrease in epp amplitude. 8. The results are discussed in terms of the theories proposed to account for the effects of osmolarity on synaptic function. Two theories--the water flow hypothesis (11) and the barrier of water hypothesis (2)--do not fit with the results. The two other theories--calcium elevation (1) and screening of surface charges (3, 13, 21)--fail to account for important aspects of the results and therfore cannot be accepted without substantial modifications. None of the theories devised to account for the increase in min epp frequency predicts the falloff in frequency and in evoked quantal release that occurs in highly hypertonic solutions.

Acetylcholine↗
PubMed1976

The effects of pH changes on the frequency of miniature end-plate potentials at the frog neuromuscular junction.

As reported by Landau & Nachshen (1975), a decrease in extracellular pH at the frog neuromuscular junction leads to an increase in min.e.p.p. frequency. 2. Decreasing the extracellular pH still increases the min.e.p.p. frequency when the bathing Ringer contains 10 mM-Ca2+, in place of the usual 2-5 mM. At the mammalian neuromuscular junction, the elevated Ca2+ blocks the effect of the pH change on the min.e.p.p. frequency (Hubbard, Jones & Landau, 1968). 3. In Cl--free solution (isethionate or methylsulphate substitution) min.e.p.p. frequency is no longer a monotonic function of decreasing pH. Instead there is an optimum pH for spontaneous release between pH 6-6 and 8-6. 4. This suggests that in Cl- containing Ringer min.e.p.p. frequency increases with increasing extracellular acidity because there is a change in the PCl of the nerve terminal leading to a depolarization. In agreement with this idea,in low Ca2+ Ringer, acid pH has little effect on the min.e.p.p. frequency. 5. Decreasing the intracellular pH by raising PCO2 produces substantial increases in the min.e.p.p. frequency. The effects are much greater than the effects of equal changes of H+ in the extracellular solution. 6. Possible explanations for the effects of increased PCO2 are discussed. Although release of Ca2+ from mitochondria or other unknown effects of intracellular pH change or molecular CO2 are possible, the results do give some support to the hypothesis that an important step in transmitter release involves an electrostatic repulsion between fixed membrane surface charges on the transmitter containing vesicles and the inner face of the nerve terminal. The surface charge density would be decreased by a lower pH in the axoplasm, and this would increase the rate of spontaneous transmitter release, in agreement with the observations.

Animals↗
PubMedDate not supplied

A new stain for quantitative measurement of sprouting at neuromuscular junctions.

A new combined stain for the simultaneous demonstration of motor nerve terminals and cholinesterase at neuromuscular junctions is described. It employs bromoindoxyl acetate dye-staining for cholinesterase and silver-gold impregnation for nerve terminals. The clarity and reliability of the stain permit quantitative measurements of neuromuscular junctions in order to evaluate nerve terminal sprouting as well as other pathological changes. The method is rapid, reproducible, and simple, and it is well suited for the processing of large numbers of frozen sections.

Botulinum Toxins↗