Showing papers on "Neurotransmission published in 1975"

Self-inhibition by dopaminergic neurons.

Abstract: Animals and Plants, L. E. Gilbert and P. H. Raven, Eds. (Univ. ofTexas Press, Austin, 1975), p. 3. 76. J. W. Hanover, Annu Rev. Entomol. 20,75 (1975). 77. R. H. Smith, U.S. For. Serv. Gen. Tech. Rep. PSW-I (1972); A. A. Berryman, BioScience 22, 598 (1972). 78. V. 1. Grimal'skii, L. T. Krushev, V. P. Gorlushkina, Lesn. Khoz. 12, 54 (1971); W. P. Smeljanez and L. A. Chursin, Anz. Schaedlingskd. 45, 33 (1972). 79. C. M. McKell, J. P. Blaisdell, J. R. Goodin, Eds., Wildland Shrubs-Their Biology and Utilization (General Technical Report INT-1, U.S. Forest Service, Washington, D.C., 1972). 80. C. H. A. Little, Can. J. Bot. 48, 1995 (1970). 81. S. J. Dina and L. G. Klikoff, J. Range Manage. 26, 207 (1973); J. D. Hodges and P. L. Lorio, Jr., Can. J. Bot. 47, 1651 (1969); see also Parker (84). 82. D. Otto, Arch. Forstwes. 19, 135 (1970). 83. W. Schwenke, Z. Angew. Entomol. 61, 365 (1968). 84. J. Parker, in Water Deficits and Plant Growth, T. T. Kozlowski, Ed. (Academic Press, New York, 1972), vol. 3, p. 125. 85. A. W. Naylor, in ibid., p. 241; R. E. Saunier, H. M. Hull, J. H. Ehrenreich, Plant Physiol. 43, 401 (1968). 86. T. C. R. White, Oecologia 16,279 (1974). 87. G. T. Harvey, Can. Entomol. 106, 353 (1974); see also Otto (82) and Schwenke (83). 88. T. T. Kozlowski, J. For. 67, 118 (1969); H. 0. Batzer, Environ. Entomol. 2, 727 (1973). 89. D. H. Janzen, Am. Nat. 104, 501 (1970); C. B. Huffaker, in Dynamics of Populations, P. J. denBoer and G. R. Gradwell, Eds. (Centre for Agricultural Publishing and Documentation, Wageningen, Netherlands, 1971), p. 327; J. R. Blais, For. Chron. 44 (1968).

Relative pre- and postsynaptic potencies of alpha-adrenoceptor agonists in the rabbit pulmonary artery.

Abstract: The rabbit pulmonary artery contains postsynaptic α-adrenoceptors which mediate smooth muscle contraction; its noradrenergic nerves contain presynaptic α-adrenoceptors which mediate inhibition of the release of the transmitter evoked by nerve impulses. Dose-response curves for the pre- and postsynaptic effects of eight α-receptor agonists were determined on superfused strips of the artery in the presence of cocaine, corticosterone and propranolol.

Calcium role in depolarization-secretion coupling: an aequorin study in squid giant synapse

Abstract: Aequorin, a protein that emits light in the presence of calcium, was injected in the presynaptic terminal of the squid giant synapse. This injection was preceded by intracellular tetraethylammonium administration, which prolonged the duration of the presynaptic action potential. After this procedure light emission was evoked by single presynaptic spikes capable of releasing synaptic transmitter. In a second set of experiments, presynaptic tetraethylammonium injection was followed by the administration of tetrodotoxin extracellularly, which abolished the presynaptic action potential. Under these conditions artificial depolarization of the presynaptic terminal triggered the release of synaptic transmitter, in a graded manner. However, as previously reported by other authors, membrane potential steps to an internal positive value of approximately plus 90 mV (the suppression potential) produced a blockage of transmitter release for the duration of the imposed potential. Synaptic transmission recurred, nevertheless, as the current injection was terminated. A similar set of experiments, performed after the intracellular injection of aequorin in the presynaptic fiber, demonstrated that the aequorin light response was evoked by membrane potential steps capable of releasing synaptic transmitter. If the membrane potential was made positive to the "suppression" level, no light response was evoked but the light emission appeared, as did transmitter release, at the end of the current pulse. These experiments demonstrate that release of transmitter is directly correlated with intracellular calcium concentration and that the suppression potential is compatible with the existence of a calcium equilibrium potential at the presynaptic terminal.

The actions of volatile anaesthetics on synaptic transmission in the dentate gyrus.

Abstract: 1. The action of four volatile anaesthetics on the evoked synaptic potentials of in vitro preparations of the hippocampus were examined. 2. All four anaesthetics (ether, halothane, methoxyflurane and trichloroethylene) depressed the synaptic transmission between the perforant path and the granule cells at concentrations lower than those required to maintain anaesthesia in intact animals. 3. The population excitatory post-synaptic potential (e.p.s.p.) and massed discharge of the cortical cells (population spike) were depressed at concentrations of the anaesthetics lower than those required to depress the compound action potential of the perforant path nerve fibres. None of the anaesthetics studied increased the threshold depolarization required for granule cell discharge. Furthermore, frequency potentiation of the evoked cortical e.p.s.p.s was not impaired by any of the anaesthetics studied. 4. It is concluded that all four anaesthetics depress synaptic transmission in the dentate gyrus either by reducing the amount of transmitter released from each nerve terminal in response to an afferent volley, or by decreasing the sensitivity of the post-synaptic membrane to released transmitted or by both effects together.

Transneuronal changes of synaptic endings and nuclear chromatin in the trapezoid body following cochlear ablations in cats

Abstract: This study demonstrates long-lasting structural changes in highly specific synaptic endings, the calyces of Held, and in the principal cells, contacted by calyces, in the medial trapezoid nucleus following acoustic deafferentation of adult cats. The normal structure of the principal cell and its afferent axosomatic endings, including the calyx and other, smaller endings, was defined in rapid Golgi impregnations and electron micrographs. Each calyciferous axon, arising from the contralateral cochlear nucleus, forms a calyx, about 35 μm in diameter, around only one principal cell body; each principal cell receives only one calyx. In electron micrographs a calycine profile typically contains a central core of neurofilaments, surrounded by mitochondria; spherical vesicles gather at multiple, asymmetric synaptic complexes. Fifteen and 30 days after unilateral labyrinthectomy the contralateral calyces showed neurofilamentous hyperplasia; mitochondria and the now enlarged synaptic vesicles decreased in number. After 30 days the contralateral principal neurons showed increased condensation of nuclear chromatin. All of these changes diminished after 56 days and were gone by seven months, when the principal cell body had shrunk by 30%. The calyx, which exhibits strongly excitatory synaptic transmission spontaneously and during acoustic stimulation, could mediate significant trophic effects. Such effects are no doubt reflected in the extensive transneuronal changes after interruption of cochlear input. These changes must involve pre- and post-synaptic alterations of protein metabolism, control of which may be linked to synaptic transmission.

Formation of cholinergic synapses between dissociated sympathetic neurons and skeletal myotubes of the rat in cell culture

Abstract: Sympathetic principal neurons, dissociated from superior cervical ganglia of newborn rats, were plated into cultures containing rat skeletal myotubes formed from previously plated primary myoblasts. Electrophysiological evidence is presented that the neurons developed cholinergic synapses with the myotubes. In addition, the neurons developed cholinergic synapses with each other as previously reported [O'Lague et al. (1974) Proc. Nat. Acad. Sci. USA 71, 3602-3606]. The acetylcholine receptors of myotubes differed from those of the neurons in their sensitivities to curare and hexamethonium, in a manner expected of adult muscle and ganglionic receptors. alpha-Bungarotoxin blocked synaptic transmission from neuron to myotube, but not from neuron to neuron in the same culture.

Effects of maintained depolarization of presynaptic neurons on inhibitory transmission in lobster neuropil

Abstract: 1. Intracellular microeleotrode recordings were obtained from somata of the pre- and postsynaptic neurons of each of four neuron pairs in the stomatogastric ganglion ofPanulirus argus. The microelectrodes were incorporated into a bridge circuit, permitting simultaneous recording and current passing. 2. The following cell pairs were investigated: I. Pyloric Dilator—Pyloric Neuron (PD-PY); II. Anterior Median—Gastric Neuron (AM—GM); III. Large BPSP—Lateral Cardiac or Posterior Gastro-pyloric (EX—LC/GP; IV. Large EPSP—Gastric Mill (EX—GM). The postsynaptic effects of current-induced variations in presynaptic membrane potential were studied in each neuron pair under a variety of experimental conditions. 2. In two cell pairs, the PD—PY and the AM—GM, action potentials initiated antidromically in the presynaptic element did not evoke postsynaptic potentials. If the postsynaptic neuron was simultaneously depolarized through the soma electrode postsynaptic potentials were observed. It is suggested that in the normal functioning of the ganglion local presynaptic depolarizations as well as spikes contribute to transmitter release. 2. In the EX—GM and the EX—LC/GM cell pairs, presynaptic depolarization that did not initiate action potentials nevertheless evoked postsynaptic inhibition and hyperpolarization for as long as the presynaptic current was maintained. Control experiments showed that presynaptic hyperpolarization had no postsynaptic effect. 2. The hyperpolarizing effect of presynaptic depolarization could be blocked by picrotoxin in parallel with blockade of other IPSPs in the ganglion. 2. The experimentally induced voltage changes in the presynaptic terminals are probably comparable to those resulting from synaptic input to the neuron. These experiments support the hypothesis that, in life, depolarization of presynaptic terminals that are subthreshold for action potentials may facilitate or evoke transmitter release. Such presynaptic, nonspike potentials may play a significant role in the modulation of synaptic transmission in neuropil.

Effects of chronic treatment with various neuromuscular blocking agents on the number and distribution of acetylcholine receptors in the rat diaphragm.

Abstract: 1. Acetylcholine receptors in the end-plate and non-end-plate areas of the rat diaphragm, after treating the animal with hemicholinium-3, alpha- or beta-bungarotoxin in vivo, were studied by their specific binding of labelled alpha-bungarotoxin. 2. Subcutaneous injection of maximum tolerable doses of hemicholinium-3 (50 mug/kg) twice daily for 7 days increased the number of extrajunctional receptors along the whole length of muscle fibre, the approximate density of receptor on muscle membrane being increased from 6/mum2 in normal diaphragm to 38/mum2. Junctional receptors were also increased in number from 2-2 x 10(7) to 2-8 x 10(7) per end-plate. 3. Five days after denervation, there were approximately 153/mum2 extrajunctional receptors and the number of receptors on the end-plate was increased by 220%. 4. Intrathoracic injection of beta-bungarotoxin (50 mug/kg) also increased the density of extrajunctional receptors to approximately 104/mum2, and the number of end-plate receptors by 140% in 5 days. The neuromuscular block was extensive and prolonged. 5. [3H]Diacetyl alpha-bungarotoxin (150 mug/kg) injected into thoracic cavity caused complete neuromuscular blockade for 12 hr. At 24 hr, the synaptic transmission was restored in 80% of the junctions with less than 10% end-plate receptors freed, whereas the safety factor for transmission in normal diaphragm was 3-5. Extrajunctional receptors appeared to increase within 24 hr. This increase continued despite the restoration of neuromuscular transmission, and the receptor density at 5 days was approximately 5l/mum2. The number of junctional receptors, however, was not increased. Repeated injection of the toxin gave the same result. 6. It is concluded that the numbers of junctional and extrajunctional acetylcholine receptors are regulated in different ways, and the possible role of acetylcholine is discussed.

Nerve terminal ATPase as possible trigger for neurotransmitter release.

Abstract: WHEN a wave of depolarisation spreads down an axon and invades the nerve terminals a number of events rapidly occur and it is difficult to establish the one ultimately res ponsible for the release of neurotransmitter. There is strong evidence to support the contention that calcium ion influx is involved both in the release of acetylcholine1 and of noradrenaline2 but ion-exchange processes at the level of the vesicle not necessarily directly involving calcium have been proposed3 and the concept of regulation of release through changes in the activity of an adenosine triphos-phatase (ATPase) has also been invoked4,5. This paper is concerned with the last possibility. Following the inward movement of sodium ions the inward movement of calcium ions to the enzyme on the inner edge of the nerve terminal membrane would be expected to inhibit the activity of sodium potassium-activated magnesium-dependent ATPase (Na,K-ATPase)6. Sodium depletion or the addition of ouabain to preparations in vitro would also be expected to inhibit Na K-ATPase activity. These three conditions of enzyme inhibition have all been shown to result in increased acetylcholine release4,5.

The action of ether and methoxyflurane on synaptic transmission in isolated preparations of the mammalian cortex.

Abstract: 1. The actions of ether and methoxyflurane on the evoked potentials of in vitro preparations of the guinea-pig olfactory cortex were studied. Following stimulation of the lateral olfactory tract (l.o.t.) evoked potentials could be recorded from the cortical surface; these potentials consisted of an initial wave (the compound action potential of the l.o.t.) followed by a negative field potential which was associated with the synchronous excitation of many superficial excitatory synapses (population e.p.s.p.). Superimposed on the population e.p.s.p. was a number of positive peaks. These positive peaks reflect the synchronous discharge of many neurones and so have been called population spikes. 2. When ether or methoxyflurane was added to the gas stream that superfused the surface of the preparations, the population e.p.s.p.s. and population spikes were depressed at lower concentrations than those required to depress the compound action potential of the afferent fibres. 3. The evoked activity of individual cells in the cortex was depressed by ether and methoxyflurane. However, five of the twelve cells tested in ether showed an increase in their evoked activity at concentrations below 4-5%, but at higher concentrations these cells also became depressed. 4. Both ether and methoxyflurane depressed the sensitivity of cortical neurones to iontophoretically applied L-glutamate and may similarly depress the sensitivity of the post-synaptic membrane to the released transmitter substance. 5. Neither anaesthetic appeared to increase the threshold depolarization required for nerve impulse generation. Thus, the decrease of the discharge of the post-synaptic cells was primarily caused by a depression of chemical transmission. 6. Ether caused some cells in the cortex to alter their normal pattern of synaptically evoked discharge and both anaesthetics induced similar changes during excitation by glutamate.

Effects of pressure and anesthetics on conduction and synaptic transmission.

Abstract: The antagonism observed between pressure and anesthesia in intact animals suggests that pressure antagonism may be a promising criterion for identifying the effects of anesthetics which are important to loss of responsiveness. It is therefore of interest to compare the effects of pressure and anesthesia on conduction and on synaptic transmission, which have often been proposed as possible alternative cellular sites of anesthesia. The model used in this study is the isolated rat superior cervical ganglion. Helium pressure (35-103 atm) antagonized partial conduction block of the preganglionic nerve by halothane(0.5 and 1 mM). Helium pressure failed to antagonize the depressant effects of halothane (0.25-0.5 mM) on nicotinic transmission and of halothane or methoxyflurane (0.24 mM) on muscarinic transmission in the ganglion. Pressure itself severely depressed synaptic transmission and added to the depressant effects of the anesthetics. Conduction block as a possible cellular mechanism of anesthesia therefore meets the proposed criterion of pressure reversibility. In contrast, pressure does not antagonize anesthetic depression of excitatory synaptic transmission in the rat superior cervical ganglion.

Motoneuron dendrites: role in synaptic integration

Abstract: Dendrites constitute over 80% of the receptive surface area in cat motoneurons. Calculations based on matched electrical and geometrical measurements in these neurons indicate that the specific resistance of dendritic membranes in resting motoneurons is at least 2,000 ohm-cm2. When the specific membrane resistance is this high, even the most distal dendritic synapses can contribute significantly to the depolarization of the soma, and hence influence the rate of action potential generation. However, dendritic membrane resistance depends strongly on the level of background synaptic activity. The conductance changes associated with excitatory synaptic activity on a dendrite can be great enough to reduce significantly both the excitatory synaptic driving potential and the effective membrane resistance on that dendrite, and thus greatly reduce the effectiveness of synapses on that dendrite. Inhibitory synaptic activity produces an even greater reduction in dendritic membrane resistance. Thus the relative effectiveness of dendritic synapses depends on the type, distribution, and intensity of background synaptic activity, as well as on dendritic geometry and resting membrane properties. —Barrett, J. N. Motoneuron dendrites: role in synaptic integration. Federation Proc. 34: 1398–1407, 1975.

Effect of Dendroaspis Neurotoxins on Synaptic Transmission in the Spinal Cord of the Frog

Abstract: Six neurotoxins from Dendroaspis venom, and $\alpha $-bungarotoxin, were tested on a cholinergic synaptic pathway in the isolated spinal cord of the frog. Four dendrotoxins, which block neuromuscular transmission, also blocked the cholinergic pathway in the spinal cord. In both cases the block is slowly reversible and not due to presynaptic action. The dendrotoxins appear to act by blocking acetylcholine receptors and are therefore potentially useful for the localization and isolation of acetyl-choline receptors in the central nervous system of vertebrates.

Changes in cholinergic synaptic vesicle populations and the ultrastructure of the nerve terminal membranes of Narcine brasiliensis electron organ stimulated to fatigue in vivo.

Abstract: Narcine brasiliensis electric organ was stimulated to fatigue in vivo. Electrical display of organ output and biochemical assay of bound acetylcholine (ACh) and ATP in isolated vesicles were used to assess the state of fatigue relative to denervated control organs of the same fish. A morphometric analysis of the fate of the synaptic vesicle populations in the nerve terminals was carried out. Statistically significant morphological changes in vesicle populations and plasma membranes were observed between control and fatigued electroplaque stacks from individual fish. Pooled data from several fish were used to evaluate the possible role of the different vesicle types in neurotransmission. Fatigue resulted in the loss of 49% of the total vesicle population and a 76% loss of vesicles with bound calcium (Ca). An approximately equivalent increase in the nerve-terminal plasma membrane area was measured. This was predominantly in the form of fingerlike protrusions and/or invaginations of the terminals which were present in the control organs but which were significantly increased by stimulation. Vesicle attachments to the nerve terminal membrane were reduced by 90%. This suggests that the failure in transmission may be due to reduction in the number of vesicles which are loaded with transmitter and can attach to the terminal membrane. The Ca-binding capacity of the lost vesicles was not transferred to the plasma membranes. This result was interpreted as support for the hypothesis that vesicle-bound ATP provides the Ca-binding site.

Synaptic transfer at a vertebrate central nervous system synapse.

Abstract: 1. The relation between presynaptic depolarization and transmitter release was examined at a synapse between a Muller axon and a lateral interneurone in the spinal cord of the lamprey. Two micro-electrodes, one for passing current and the other for recording the resulting voltage change, were placed in the presynaptic axon; a single electrode for recording the post-synaptic potential produced by release of transmitter was placed in the post-synaptic cell. 2. When action potentials were blocked with tetrodotoxin, brief depolarizing pulses in the presynaptic fibre were as effective as the action potential had been in producing transmitter release. 3. The release process had an apparent threshold depolarization of 40-50 mV and saturated at presynaptic depolarizations of the order of 100 mV. Increasing the duration of the presynaptic pulse increased the maximum level of release. 4. Displacing the presynaptic voltage recording electrode from the position of synaptic contact toward the current passing electrode increased the apparent depolarization required to produce a given level of transmitter release. This shift in the input-output relation was consistent in magnitude with the voltage attenuation between the presynaptic recording electrode and the synapse expected from the space constant of the fibre. 5. The effect of conditioning hyperpolarization and depolarization of the presynaptic fibre on subsequent transmitter release by brief depolarizing pulses was examined. No effect was observed when the presynaptic recording electrode was in the region of synaptic contact. When the presynaptic electrode was not so positioned, conditioning effects were observed which depended on electode position and could be attributed to changes in the space constant of the presynaptic fibre. No conditioning effects were observed on transmitter release by the action potential.

An electrophysiological analysis of the effect of Ca ions on neuromuscular transmission in the mouse vas deferens.

Abstract: 1 A study has been made of the effects of changing the external calcium concentration [Ca]0 and the external magnesium concentration [Mg]0 on the synaptic potential due to noradrenaline release. 2 When [Ca]0 was varied in the range 0.7 to 1.8 mM, the synaptic potential increased as about the second power of [Ca]0. 3 Increasing [Mg]0 depressed the synaptic potential; however, variation of [Ca]0 in the presence of high [Mg]0 did not significantly change the power relationship between the synaptic potential and [Ca]0. 4 The facilitated increase in the synaptic potential during short trains of impulses at different frequencies was quantitatively predicted on the assumption that each impulse leaves residual Ca ions bound to release receptors in the nerve terminal.

Tonic release of transmitter at the neuromuscular junction of the crab.

Abstract: 1. Synaptic transmission was studied at the neuromuscular junction of the crab Ocypoda cursor, using conventional electrophysiological technique. 2. It was found that fibres of the extensor muscle and those composing the internal layer of the closer muscle have only post-synaptic inhibition (S fibres) while the fibres at the external layer of the closer muscle have in addition presynaptic inhibition (R fibres). 3. In S fibres, addition of GABA reduces input membrane resistance (Rm) and e.p.s.p. amplitude approximately to the same degree. The effect shows desensitization. In R type fibres, GABA reduces the e.p.s.p. much more than expected from changes in Rm. The post-synaptic effect of GABA on Rm shows desensitization, while the presynaptic effect does not show desensitization. 4. In about 50 percent of the cases, after desensitization occurred, Rm increased by about 10-30 percent above the control. Similar increase in Rm occurred after application of picrotoxin. These results suggest that initially the membrane resistance was lower due to tonic release of inhibitory transmitter. 5. The Q10 of Rm was found to vary between 2 and 3. In Ca2+ free media, Cl- free media, or in picrotoxin the Q10 is about 1-3. 6. In R fibres, addition of picrotoxin increased the amplitude of the e.p.s.p. by 30-60 percent above the expected increase due to changes in Rm. 7. In S fibres the mean slope of log e.p.s.p. vs. log [Ca2+] was found to be 1-63, while in R fibres the slope was 0-93. These results suggest the presence of tonic release of the inhibitory transmitter which acts both post-synaptically and presynaptically.

A pharmacologic study of the stiff‐man syndrome Correlation of clinical symptoms with urinary 3‐methoxy‐4‐hydroxy‐phenyl glycol excretion

Abstract: We have investigated hypotheses that link the stiff-man syndrome to an imbalance of neurotransmitter systems. No evidence was found to support the concept of defective synaptic transmission at either cholinergic input to Renshaw inhibitory elements or at glycinergic inhibitory input to motoneurons from spinal interneurons, since neither physostigmine nor glycine altered symptomatology. Urinary excretion of the norepinephrine metabolite 3-methoxy-4-hydroxy-phenyl glycol showed a high correlation with clinical status. This suggests the involvement in the stiff-man syndrome of a central norepinephrine neuronal system that has net excitatory effects upon motoneurons, a system whose activity can be increased slightly by levodopa and decreased markedly by diazepam, with corresponding changes in stiffness.

Genetically-associated variations in the development of reflex movements and synaptic junctions within an early reflex pathway of mouse spinal cord.

Abstract: The embryonic development of reflex forelimb movements produced by cutaneous stimulation of the forepaw was examined in five inbred strains of the house mouse, Mus musculus. A quantitative electron microscopic study of synapse formation between the neurons that comprise the spinal cutaneous reflex arc was also carried out on specimens from three of the strains subjected to reflex testing. This investigation provides evidence that there is significant genetically-associated variability in the developmental timing of synapse formation within this disynaptic pathway and in the reflex behavior which it mediates. Specifically, it was found that C57BL/6J embryos had greater numbers of synaptic junctions in the reflex pathway at embryonic days 14–16, and they also showed reflex movements earlier than LP/J embryos. C57BL/6J embryos also showed a more rapid increase in the number of boutons during this embryonic period. CBA/CaJ embryos displayed a temporal pattern of development that differed from both C57BL/6J and LP/J. At E15, CBA/CaJ embryos were more similar to LP/J with regard to both reflex activity and synapse number, but by E16, CBA/CaJ values for both of these measures were more similar to C57BL/6J. On the basis of the data detailed in the text, we suggest that the strains differ in the following manner: C57BL/6J embryos develop boutons rapidly but appear to be relatively inefficient in the actual formation of synaptic junctions; CBA/CaJ embryos develop boutons at a slower rate than C57BL/6J but form synaptic junctions more efficiently; LP/J embryos develop boutons slowly and are also relatively inefficient in forming synaptic junctions. The genetic implications of — and some developmental processes which might be responsible for — the observed strain differences in the timing of synaptic development are discussed in the text. There was no detectable genetic variability of the basic sequence in which the neurons of the cutaneous reflex arc develop their synaptic connections. For all three strains examined, the data indicated that synaptic closure occurred in a retrograde sequence with respect to the direction that neurotransmission normally flows between the neurons of this pathway. This finding agrees with results obtained by other investigators from a number of diverse vertebrate species, and such a widespread lack of variability implies that a retrograde sequencing of synapse formation is involved in the development of specific neuronal connectivities.

An electrophysiological analysis of the effects of reserpine on adrenergic neuromuscular transmission.

Abstract: 1 An electrophysiological study has been made of the effects of depleting synaptic vesicles (i.e. small vesicles less than 60 nm diameter) of their transmitter with reserpine on the quantity of transmitter released by nerve impulses, using the amplitude of the synaptic potential as a measure of transmitter release. 2 Pretreatment of adrenergic nerve terminals with reserpine sufficient to deplete the terminals of 70% of their noradrenaline (NA) did not change the total number of synaptic vesicles in the terminals, but did reduce the number with a large granular core as well as the quantity of NA released by a single nerve impulse by 80%. 3 Pretreatment of adrenergic nerve terminals with reserpine and iproniazid, to decrease vesicular NA but enhance cytoplasmic NA, had the same effect on synaptic vesicles and on the NA released by a single nerve impulse as did reserpine alone. 4 During a short train of impulses at high frequencies in reserpine pretreated terminals, the quantity of NA released by successive impulses increased until a steady-state release was reached comparable to that in untreated preparations. This facilitated release could be quantitatively predicted in terms of the addition of the individual potentiations introduced by each impulse in the train. 5 These results are consistent with the idea that each quantum of transmitter is stored in a synaptic vesicle, and that these may be released by nerve impulses directly from the terminal by a process of exocytosis.

Comparative site of action of various anaesthetic agents at the mammalian myoneural junction

Abstract: SUMMARY Pre- and postjunctional effects of three ethers (enflurane, diethyl ether, and methoxyflurane) and three non-ethers (chloroform, halothane, and trichloroethylene) were studied in the rat phrenic nerve diaphragm preparation using standard microelectrode recording techniques. Depression of postjunctional function included depression of the amplitude of miniature endplate potentials, inhibition of suxamethonium induced depolarization of the muscle endplate, prolongation of duration of the endplate potential, and increase in threshold for generation of the muscle action potential. The last two effects were more marked for the ethers than for the non-ethers. Effects on prejunctional function included a slight increase in fluctuation of the endplate potential (EPP) amplitude associated with the ethers and chloroform, a faster rate of decline of EPP amplitude during a tetanus in presence of the ethers, and prolongation of the normal facilitatory period during paired stimulation in the presence of chloroform. Chloroform had no effect on the rate of decline of EPP amplitude during tetanic stimulation and the ethers had no effect on the facilitatory period during paired stimulation. These results indicate that volatile anaesthetic agents depress synaptic transmission by acting on multiple sites, and that the pattern of this depression is different for each drug or group of similar drugs.