PubMed Health⌕ Search

Biomedical subjects

N Tabti

Publications and source records attributed to N Tabti.

13 recordsLinked to original sources
PubMed1992

Pulsatile release of acetylcholine by nerve terminals (synaptosomes) isolated from Torpedo electric organ.

1. Electrophysiological detection of acetylcholine (ACh) release by synaptosomes from the electric organ of Torpedo was searched for by laying the isolated nerve terminals on a culture of Xenopus embryonic muscle cells (myocytes), and by recording the ACh-induced inward currents in the myocytes. 2. Whole-cell recording in one of the myocytes revealed rapid inward currents that where generated soon after synaptosome application. These pulsatile events strongly resembled those occurring normally during the early phase of synaptogenesis after nerve-muscle contact in Xenopus cell cultures. They were called spontaneous synaptic currents (SSCs). 3. The SSCs produced by the synaptosomes had a rapid time course, with mean time-to-peak and half-decay times of 2.6 +/- 0.4 ms and 6.0 +/- 1.1 ms, respectively. Most events had a falling phase that could be fitted with a single exponential. The mean time constant of decay was 6.2 +/- 1.1 ms. More than half of the SSCs (approximately 60%) constituted a rather homogenous population in which the time-to-peak versus amplitude showed a positive relationship, the smallest events displaying a shorter time course. The rest of the SSCs had a more variable and slower time course. Such events are also observed in young and mature junctions in situ. 4. The amplitudes of SSCs had a wide distribution which was skewed towards the smallest values. The mean amplitude was 65.2 +/- 16.1 pA. 5. During the minutes following an application of synaptosomes, the frequency of the SSCs tended to decrease, but their mean amplitude remained constant. Such behaviour could be reproduced during several successive additions of synaptosomes while recording in the same myocyte. 6. Just after synaptosome application, the SSCs were superposed to a noisy inward current that lasted for 20-60 s. Noise analysis of this current gave the values of 0.7 +/- 0.1 pA for the mean amplitude of the elementary event, and 4.7 +/- 0.2 ms for its mean duration, values that compare well with those reported for the activation of frog embryonic nicotinic receptor. This suggests that the noisy current was due to ACh molecules set free by synaptosomes which were either damaged or which released ACh at some distance. This view was strengthened by biochemical analysis of ACh release by synaptosomes in vitro. 7. Tubocurarine reversibly abolished the appearance of both the noise and the synaptosome-generated SSCs, showing that these currents were due to the action of ACh.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1990

Terminal sprouting in mouse neuromuscular junctions poisoned with botulinum type A toxin: morphological and electrophysiological features.

Functional properties of terminal sprouts elicited by an in vivo injection of Clostridium botulinum type A toxin were studied in endplates of the Levator auris longus muscle of the mouse poisoned from a few days to 28 days beforehand. For this purpose, morphological observations of the extent of terminal sprouts and localization of acetylcholine receptors was performed in whole mount preparations. Sprouts appeared as thin unmyelinated filaments that run usually parallel to the longitudinal axis of the muscle fibres; labelling acetylcholine receptors revealed their line-shaped accumulation co-localized with the sprouts. In addition, presynaptic membrane currents elicited by nerve stimulation were recorded by external electrodes applied under visual control onto the membrane of pre-existing motor endings and newly formed sprouts. These recordings showed the presence of widespread triphasic waveforms which indicated active impulse propagation of the action potential over most of the length of the poisoned endings. Ca2+ influx and Ca2(+)-dependent K+ currents in the sprout membrane were found to be similar to those described in unpoisoned endings. The presence of normal Ca2+ influx, upon active depolarization, in the terminal sprout membranes together with the localization of acetylcholine receptors in front of these membranes, indicates that the terminal sprouts may play a role in the recovery of neuromuscular transmission after Clostridium botulinum poisoning.

4-Aminopyridine↗
PubMed1990

Presynaptic actions of botulinal neurotoxins at vertebrate neuromuscular junctions.

1. In the present paper we review some presynaptic aspects of the mode of action of botulinal toxins (BoTxs) at vertebrate neuromuscular junctions with emphasis on studies carried out in our laboratories using electrophysiological and morphological techniques. 2. Spontaneous quantal transmitter release recorded as miniature end-plate potentials is drastically affected by BoTxs. The low probability of release at poisoned terminals can be enhanced by carbonyl cyanide m-chlorophenylhydrazone (CCCP), Cd2+ and La3+. However, CCCP and La3+ which drastically deplete clear synaptic vesicles from unpoisoned terminals failed to markedly affect the density of synaptic vesicles at poisoned terminals. It is concluded that poisoned terminals have a reduced sensitivity to the release-promoting action of Ca2+, Cd2+ and La3+. 3. When comparing the effect of the various BoTxs on nerve-impulse evoked transmitter release it appears that increasing phasic Ca2+ entry into the terminals enhances evoked synchronized quantal release only from terminals poisoned with serotypes A and E. In contrast, enhanced Ca2+ entry into terminals poisoned with serotypes B, D and F induced a period of high frequency asynchronous release suggesting that these BoTxs may affect a presynaptic step beyond the influx of Ca2+, that may be involved in the synchronization of transmitter quanta. These data suggest that the actions of BoTxs involve several steps of the acetylcholine release process. 4. The analysis of presynaptic currents which depend on both Ca2+ entry and intraterminal background Ca2+ levels strongly suggests that neither Ca2+ entry nor intraterminal Ca2+ levels are altered by BoTxs. Furthermore, poisoned terminals are no more efficient than unpoisoned ones in dealing with Ca2+ overloads. 5. Finally, the morphological examination of junctions paralysed by BoTx-A indicates that the toxin triggers a particularly important overgrowth of the nerve terminals and suggests that the in vivo functional recovery may occur from an extension of the original nerve terminal arborization and the concomitant remodelling of postsynaptic structures.

Animals↗
PubMed1989

Three potassium currents in mouse motor nerve terminals.

A study of the K conductance of the presynaptic membrane has been performed in the triangularis sterni muscle of the mouse. External currents generated in the presynaptic terminals upon invasion by action potentials have been recorded using microelectrodes inserted into the perineurium of preterminal nerve bundles. The voltage-dependent K current could be pharmacologically dissected into fast (IKf) and slow (IKs) components. While both are sensitive to 3,4-diaminopyridine (3,4-DAP), only IKf is sensitive to tetraethylammonium (TEA). Uranyl (100-200 microM) and guanidine (5-10 mM) produced a near complete block of IKf and IKs, which can explain their facilitatory effect upon transmitter release. The third K current of presynaptic terminals is Ca2+-dependent, but was activated also by Sr2+. This current could be suppressed by nanomolar doses of charybdotoxin; it is also sensitive to TEA but not to 3,4-DAP, uranyl or guanidine.

4-Aminopyridine↗
PubMed1989

A study of synchronization of quantal transmitter release from mammalian motor endings by the use of botulinal toxins type A and D.

1. The effects of botulinum toxin (BoTx) types A and D on spontaneous and evoked phasic transmitter release were studied in the isolated extensor digitorum longus muscle of the rat or the levator auris longus muscle of mice. 2. The toxins were injected subcutaneously into the hindleg of adult rats or the dorsal aspect of the neck of mice. At various times after the injection the muscles were removed from the anaesthetized animal and neuromuscular transmission examined in vitro by conventional intracellular techniques. 3. Both toxins reduced spontaneous transmitter release recorded as the frequency of miniature end-plate potentials but BoTx type D was less effective in that respect than the type A toxin. 4. With both toxins the block of evoked phasic transmitter release, recorded as end-plate potentials, was almost complete. As previously reviewed by Simpson (1986) the block produced by BoTx type A was partially reversed by procedures which elevate the intraterminal level of calcium ions. However, in BoTx type D-paralysed muscles such procedures failed to restore phasic transmitter release but caused a period of high-frequency asynchronous transmitter release following each nerve impulse. 5. To investigate if the lack of synchronization of evoked transmitter release observed in BoTx type D-paralysed muscles was due to alterations in presynaptic currents we examined, by perineural recordings, the Na+, fast K+, slow K+, K+-Ca2+-dependent and the Ca2+ currents in BoTx type D-paralysed muscles. These presynaptic currents were not altered as compared to unpoisoned controls. 6. We suggest that there exists a presynaptic process, which in addition to Ca2+ influx participates in transmitter synchronization and which is a main target for BoTx type D action.

4-Aminopyridine↗
PubMed1989

A review on drugs and toxins affecting presynaptic K+ currents and phasic quantal transmitter release at motor nerve terminals.

This review assembles available information concerning drugs and toxins which block the different types of presynaptic K+ currents and discusses the relative importance of these currents in controlling phasic quantal transmitter release. Drugs and toxins which block the fast voltage-dependent potassium current (IKf), enhance phasic acetylcholine release evoked by nerve impulses. This effect is due to increased Ca2+ influx during prolonged presynaptic membrane depolarization. Selective blockade of the Ca(2+)-dependent K+ current (IK(Ca)) does not induce any change in phasic transmitter release indicating that, under physiological conditions, IK(Ca) has no significant role in presynaptic membrane repolarization. The contribution of the slow voltage-dependent K+ current (IKs) to the regulation of phasic acetylcholine release remains to be clarified. In conclusion, IKf, IK(Ca) and IKs can modulate the entry of Ca2+ into motor nerve terminals. However, under physiological conditions only IKf plays a key role in controlling the transient Ca2+ influx which is responsible for the phasic transmitter release.

Action Potentials↗
PubMed1986

Facilitation, augmentation and potentiation of transmitter release at frog neuromuscular junctions poisoned with botulinum toxin.

Botulinum toxin type A (Botx) is a potent neurotoxin which inhibits specifically cholinergic synaptic transmission by an unknown mechanism. In order to gain further insight into the mode of action of this toxin, the effect of conditioning nerve stimuli on neuromuscular transmission was studied at endplates of Botx-poisoned and unpoisoned control cutaneous pectoris muscles in the frog. Effects of single conditioning stimuli (facilitation) and multiple high-frequency stimuli (augmentation and potentiation) on epp amplitude and mepp frequency were studied. The main results were that initial facilitation was significantly increased and its decay time constant significantly decreased in Botx-poisoned muscles, while augmentation was unchanged and potentiation was abolished. These changes could be detected before the muscle became completely paralysed, suggesting that they reflect a primary disturbance in the Ca2+-dependent release process.

Animals↗
PubMed1986

Pharmacological characterization of the calcium-insensitive, intermittent acetylcholine release at the rat neuromuscular junction.

A variety of pharmacologically active compounds was surveyed for effects on the Ca2+-insensitive miniature end-plate potentials (slow mepps) induced by botulinum toxin type A (Botx) poisoning in rat muscle. The purpose was to gain insight into the release process responsible for this type of acetylcholine secretion. It was found that caffeine and dibutyryl cyclic adenosine 3',5'-monophosphate increased significantly the frequency of slow mepps in Botx-poisoned muscles, but had no effect on slow mepps in control muscles. Vinblastine and cytochalasin B significantly increased the slow mepp frequency in Botx-poisoned as well as in normal control muscles. Inhibitors of oxidative metabolism reduced the frequency of slow mepps by 90%, indicating a high energy requirement for this type of release. No agent was found to augment the slow mepp frequency above 1-2 Hz, suggesting that an upper limit exists for this type of packaging and release of acetylcholine.

Acetylcholine↗
PubMed1986

The nature and origin of calcium-insensitive miniature end-plate potentials at rodent neuromuscular junctions.

1. To study the nature and origin of slow-rising, Ca2+-insensitive miniature end-plate potentials (m.e.p.p.s) in mammalian muscle we used intracellular recording techniques and drugs which block acetylcholine (ACh) synthesis or the uptake of ACh into synaptic vesicles. Slow m.e.p.p.s were induced in vivo by paralysing the extensor digitorum longus muscle of the rat with botulinum toxin type A or in vitro by the application of 4-aminoquinoline to the mouse diaphragm nerve-muscle preparation. 2. Hemicholinium-3, which blocks ACh synthesis, reduced the amplitude of all synaptic potentials including slow m.e.p.p.s, but only if the nerve was stimulated. 3. 2(4-phenylpiperidino)cyclohexanol (AH-5183), which blocks the active uptake of ACh into synaptic vesicles, reduced both the frequency and the amplitude of slow m.e.p.p.s and did so without requiring nerve stimulation. 4. No correlation was observed between the molecular leakage of ACh from the motor nerve and the frequency and amplitude of slow m.e.p.p.s. 5. We conclude that slow m.e.p.p.s are caused by the release of ACh from the nerve terminal, possibly from a small pool of synaptic vesicle-like structures.

Acetylcholine↗
PubMed1984

Electrophysiological studies of the sciatic nerves in Mycobacterium leprae foot pad-injected rats.

This study tested the possibility of developing an experimental model of neuropathy in female Wistar rats inoculated with Mycobacterium leprae in the foot pad and assessed by repeated electrophysiological methods. M. leprae multiplied in the rats but considerably less than in simultaneously inoculated mice. No acid-fast bacilli were found in nerves. Motor and sensory conduction velocities remained normal at the thigh level of the sciatic nerve. At the leg, they decreased significantly bilaterally for motor conduction and in the inoculated side for sensory conduction at 21 months after inoculation. These results suggest the possibility of developing an experimental model of leprosy neuropathy which might be useful for therapeutic research. Further histopathological studies are needed to assess this paucibacillary model.

Animals↗
PubMed1982

[Detection of peripheral diabetic neuropathy. A reappraisal of electrophysiological data].

In addition to motor and sensory nerve conduction, monosynaptic triceps surae reflex, amplitude of median nerve voltage and response of extensor digitorum brevis and soleus muscles were investigated in 29 diabetic patients. These parameters were altered earlier than motor and sensory nerve conduction, which considerably increased the incidence of subclinical peripheral neuropathy (90% of the patients). It was also found that sensory fibers were affected earlier than motor fibers. The electrically detected neuropathy correlated with duration of diabetes and control of glycaemia.

Axons↗