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Biomedical subjects

A Mallart

Publications and source records attributed to A Mallart.

At least 55 records · Page 3Linked to original sources

Electrical activity at motor nerve terminals of the mouse.

1. Extracellular recording of the electrical activity of mammalian end-plate made it possible to distinguish three different parts on the presynaptic terminal. Bath or ionophoretic application of ionic channel blockers induced specific alterations of electric signals which revealed the localization of classical ionic channels. 2. Sodium channels are restricted to a small area, sharply located after the end of the last myelinated segment and potassium channels are distributed over the rest of the terminal branches. 3. The first direct evidence of the presence of calcium channels at the terminal part of the motor endings was obtained, when potassium channel activity was suppressed. They occupy the same region as potassium channels. 4. Finally, the differential distribution of ionic channels over the terminal and the time-course of calcium current are discussed in relation to transmitter release.

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Advantages of the triangularis sterni muscle of the mouse for investigations of synaptic phenomena.

The triangularis sterni muscle (TS) of the mouse is a thin trapezoidal sheet of fibres in which individual neuromuscular junctions are easily observed with Nomarski optics. Thus, microelectrodes are readily positioned to accurately record various synaptic phenomena. For example, miniature end-plate currents were easily recorded with a focally positioned extracellular electrode and the end-plate sensitivity to acetylcholine averaged 2062 mV/nC. In addition, the intercostal nerves segmentally innervate the TS. Electrophysiologic and histologic analysis showed that each nerve innervates a sharply defined territory of the muscle surface. These preliminary observations suggest that the TS may be ideal for studies of synaptic function and the processes underlying synapse stabilization in the mammal.

Acetylcholine↗

Patterns of motor innervation in the pectoral muscle of adult Xenopus laevis: evidence for possible synaptic remodelling.

1. An anatomical and electrophysiological study was performed on the pectoral muscle of Xenopus laevis. 2. Silver-impregnated preparations revealed immature endings, collateral and terminal sprouting and signs of synaptic regression. 3. Twenty percent of the fibres received a dual innervation from two different nerves. The synapses of 25% of these fibres are formed in close vicinity. 4. Some of the singly innervated and most of the dually innervated end-plates generated only subthreshold electrical activity. Synaptic efficacy in dually innervated muscle fibres with closely spaced or distant endings was, on the average, one third and two thirds, respectively, of that obtained in singly innervated fibres. 5. Fibres with subthreshold electrical activity displayed normal ACh sensitivity. 6. The existence of non-transmitting synapses, of dually innervated end-plate sites and of morphological signs of the sprouting of new endings and the degeneration of old ones suggests that synaptic remodelling may occur in normal adult muscles.

Acetylcholine↗

Interaction between motor axons from two different nerves reinnervating the pectoral muscle of Xenopus laevis.

1. An electrophysiological and morphological study of sprouting and regeneration of motor nerves has been performed in the dually innervated pectoral muscle of Xenopus laevis. 2. Section of one of the nerves induced axon sprouting in the intact nerve. Synapse formation by the sprouting axons was slow since the intact nerve took more than 3 months to increase its field of innervation by 70%. The rate of axon regeneration was faster than that of axon sprouting since the cut nerve reinnervated its former territory in less than 1 month. 3. At early stages of synapse formation the sprouted or regenerated endings were poorly branched but any terminal branches were, as a rule, longer than normal. Signs of degeneration and replacement of endings have been observed. 4. Low levels of transmitter release persisted for several months in newly formed endings. This depression was more pronounced at the endings formed outside the normal field of innervation of the nerve. 5. Poly-innervated muscle fibres have been observed during reinnervation by regenerated or sprouted axons. Their number decreases gradually in the months that follow the beginning of reinnervation. Synaptic efficacy was lower at poly than at mono-innervated muscle fibres. At doubly innervated spots and at separated spots on the same fibre average end-plate potential (e.p.p.) amplitude was 1/3 and 2/3 respectively of that recorded at singly innervated fibres. 6. Electrophysiological and morphological data have been compared at individual doubly innervated end-plate sites. End-plate potential amplitude was positively correlated with the degree of ending development. 7. Sprouted endings remain functional after periods of reinnervation of 30 months, although signs of regression have been observed. These are probably mediated by spontaneous degeneration of the terminals and replacement by endings from the regenerating nerve.

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Dual innervation of end-plate sites and its consequences for neuromuscular transmission in muscles of adult Xenopus laevis.

1. Electrophysiological study of dually innervated end-plate sites was carried out in Xenopus laevis pectoral muscle fibres. End-plate potentials (e.p.p.s) and miniature end-plate potentials (m.e.p.p.s) have been recorded in Mg-blocked preparations. 2. The mean quantal content (m) of each e.p.p. at dually innervated end-plates was significantly smaller than the corresponding values obtained at singly innervated ones. At a given doubly innervated end-plate site the values of m tended to be inversely related, so that the compound value of m (obtained by adding them) was in the same range as that found in singly innervated junctions. These findings were taken to suggest the existence of an upper limit in the average amount of transmitter released at a synaptic site. 3. It was found that neither intermittent presynaptic conduction block, nor particular muscle fibre properties could account for the low values of m in dual end plates. The small size of the nerve terminals appears to be the most likely explanation. 4. The sensitivity to acetylcholine and muscle fibre electrical properties were investigated; no differences were found between fibres with sub- or suprathreshold e.p.p.s. 5. The nature of the factors responsible for this presumed small size of the nerve endings (competition between nerve endings for a limited synaptic space on the muscle membrane or reciprocal interaction between closely located terminals) as well as the possible origins of polyinnervation are discussed.

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The effects of pH and curare on the time course of end-plate currents at the neuromuscular junction of the frog.

1. The effect of pH changes on synaptic currents has been analysed by external recording of the miniature end-plate currents (m.e.p.c.s) or by recording in voltage-clamped end-plates the current elicited by nerve stimulation (e.p.c.). 2. Changes in pH do not appreciably effect the peak amplitude of the current produced by a single quantum or by short ionophoretic pulses of acetylcholine. 3. The time constant of decay of the m.e.p.c.s is prolonged by about 50% in acid pH and shortened by about the same amount in alkaline pH. This effect is independent of the cholinesterase activity of the end-plate. 4. In curarized preparations the decay of the e.p.c. is shorter than in Mg-blocked end-plate even in the absence of cholinesterase blocking agents. 5. The action of pH on the decays can be explained by a titration of the surface charges of the membrane which effects the voltage dependent reaction that controls the rate of closing of the synaptic channels.

Animals↗

Current-voltage relation and reversal potential at junctional and extrajunctional ACh-receptors of the frog neuromuscular junction.

The relationship between synaptic current and membrane potential has been examined at junctional and extrajunctional end-plate receptors of the frog. At junctional receptors, the synaptic current-membrane potential relationship is linear for close range iontophoretic ACh application and non-linear when it is delivered from some distance. At extra-junctional receptors the current-voltage relationship is always non-linear. These non-linearities can be related to the fact that in both cases [ACh] on membrane outlasts the mean life-time of the synaptic channels. When their mean life-time is varied, the current-voltage relationship obtained at junctional receptors is no longer linear and the peak synaptic conductance increases or decreases with hyperpolarization as the channel life time is shortened or lengthened, respectively.

Acetylcholine↗

Ionic properties of the neuromuscular junction of the frog: effects of denervation and pH.

1. The effects of denervation, reinnervation and pH on the ionic permeability changes mediated by junctional receptors have been studied in muscle fibres of the frog sartorius.2. The reversal potential of acetylcholine responses in denervated junctions was about 25 mV more negative than in normal junctions.3. The delay of the change in the ionic properties of junctional receptors was proportional to the nerve stump length: 10 and 14 days for lengths of 12 and 33 mm, respectively.4. When the motor nerve reinnervates the junction, the reversal potential of the acetylcholine responses comes back to the normal value before the neuromuscular transmission is restored.5. The Na/K conductance change decreases in high pH solutions. After denervation, the pH profile of this ratio is shifted to the acid values by about two pH units.6. These observations can be explained by assuming that the Na and K channels differ by the pK of their anionic groups and that the denervation induces an alteration of the sites that bear the charges.

Acetylcholine↗

An analysis of acetylcholine responses of junctional and extrajunctional receptors of frog muscle fibres.

1. An analysis has been made of the distribution and rise time of the responses induced by electrophoretic application of ACh on junctional and extrajunctional receptors of the neuromuscular junction of the frog.2. The junctional and the extrajunctional responses appear to constitute two independent groups with no overlapping characteristics: (a) the responses evoked from junctional receptors show always a high ;sensitivity' (30-100 mV/nC) and a rise time usually shorter than 10 msec that does not lengthen as the ACh dose is increased; (b) the responses evoked from extrajunctional area show a lower sensitivity (0.5-10 mV/nC) and a slow rise time that is a linear function of the dose Q((2/3)) of ACh.3. The lengthening of the rise time of extrajunctional response with increasing doses of ACh is interpreted by supposing that larger doses saturate larger areas of a membrane of low sensitivity uniformly covered with receptors. On the contrary, at junctional spots the does of ACh would be insufficient to saturate the receptors and rise time will be independent of dose.4. Relatively unresponsive zones may exist between junctional spots and extrajunctional areas and between neighbouring extrajunctional areas.5. Extrajunctional areas are subjected to significant seasonal variations; in summer they are practically absent, in autumn they appear as elongated areas of about 20 mu wide and 50 mu long, and late in winter they fuse together and all the ;end-plate' zone becomes sensitive to ACh.

Acetylcholine↗

Ionic permeability changes induced by some cholinergic agonists on normal and denervated frog muscles.

1. The reversal potential of responses to iontophoretic application of acetylcholine, carbamylcholine and decamethonium has been measured at junctional and extrajunctional sensitive areas of the normal sartorius muscle of the frog.2. The values obtained with any one of the drugs at junctional spots were similar to those previously reported for the end-plate potential (about - 16 mV).3. On the other hand, at extrajunctional areas the reversal potential of responses to these agonists was found to have a mean value of - 42 mV. The muscle-tendon responses to acetylcholine reversed at - 51 mV.4. The response to decamethonium was used to determine the nature of the ionic permeability changes mediated by the extrajunctional receptors. The results obtained show that extrajunctional responses are due to an increase in conductance to Na(+) and K(+) but not to Cl(-).5. The reversal potential of acetylcholine responses in denervated frog sartorius was - 42 mV both at former junctional spots and at non-neural sensitized regions.6. These different values of the reversal potential can be due either to effects of receptor density on the ionic selectivity of the membrane or to regional variations in the extracellular ionic accumulation during the transmitter action.

Acetylcholine↗

Thalamic projection of muscle nerve afferents in the cat.

1. Evoked responses on stimulation of hind- and forelimb muscle nerves have been recorded in the ventro-postero-lateral (VPL) and centre median (CM) nuclei of the thalamus of the cat.2. The stimulation of hind-limb muscle afferents with increasing strength usually did not evoke a thalamic response, either in the CM or in the VPL, until the threshold for Group III muscle afferents was reached.3. Short latency potentials were evoked in the VPL on stimulation of low threshold Group I muscle afferents from forelimbs. The projection zone occupies the dorso-medio-rostral part of the nucleus.4. An attempt was made to locate the medullary relay for forelimb Group I afferents either in the lateral part of the cuneate or in external cuneate.5. Low threshold afferents from forelimb muscle nerves do not project to the CM. CM responses began to appear only when the threshold for Group II muscle nerve fibres was reached.6. Group II afferents from hind- or forelimb muscle nerves projecting to the CM are probably not connected to spindle secondary endings.7. The role played by muscle afferents in the somesthetic mechanisms is briefly discussed.

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The relation between quantum content and facilitation at the neuromuscular junction of the frog.

1. Experiments were done on the neuromuscular junction of the frog to study facilitation of the end-plate potential (e.p.p.) produced by one or more conditioning shocks applied to the motor nerve. Neuromuscular transmission was blocked with Mg (+)-tubocurarine chloride.2. In Mg-blocked preparations, facilitation increased with increasing Mg concentrations in the range 14-34 mM. The increase in facilitation was related specifically to the decrease in mean quantum content of the e.p.p., and was most marked with quantum contents less than 10.3. Facilitation in curarized preparations was similar in magnitude to that in preparations blocked with the lower Mg concentrations. Interaction between facilitation and depression in curarized preparations was consistent with the idea that facilitation was due to an increase in probability of transmitter release and depression to depletion of transmitter.

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