Search PubMed⌕ Search

Biomedical subjects

L Tauc

Publications and source records attributed to L Tauc.

At least 73 records · Page 4Linked to original sources
PubMed1986

The quantal release at a neuro-neuronal synapse is regulated by the content of acetylcholine in the presynaptic cell.

Transmitter release was studied with respect to the presynaptic acetylcholine (ACh) content at a central identified inhibitory synapse (Cl- conductance) of Aplysia californica. Statistical analysis of the synaptic noise evoked by sustained depolarization of the presynaptic neuron allowed us to calculate the quantal parameters of the postsynaptic responses. Loading of the presynaptic neurone with injected ACh led to an increase in the postsynaptic responses whereas the calculated miniature postsynaptic current (MPSC) was unmodified. Destruction of choline by choline oxidase either applied extracellularly and coupled to intense stimulations of the presynaptic cell or injected into the presynaptic neuron induced a depression of the postsynaptic response although the amplitude of the calculated MPSC remained constant. As the size of the MPSC, i.e. the size of the quantum, did not change in these experiments, it was concluded that the presynaptic ACh content controls the number of quanta released by a given presynaptic depolarization. As additional evidence, effects of abrupt increase in tonicity of the external medium were studied. The observed transient enhancement of the quantal content of the postsynaptic response could be attributed to an increase in the presynaptic concentration of ACh, resulting from the reduction in cellular volume.

Acetylcholine↗
PubMed1985

Development of ionic channels during mouse neuronal differentiation.

Using a mouse embryonal teratocarcinoma (E.C.) cell line, it was possible to follow the sequence of development of ionic channels during neuronal differentiation, with patch-clamp techniques. 1003 E.C. cells were induced to differentiate into neurons by culturing them in defined medium without foetal calf serum (DARMON et al., 1981). Non-differentiated cells were not excitable and presented mainly 2 types of K+ channels: a Ca2+ activated K+ channel (220 pS in symmetrical K+) and a delayed rectifier (30 pS in symmetrical K+). When the cells start to grow neurites, a low threshold calcium current can be recorded, only if the cell is held at hyperpolarized potentials (-70 to -80 mV). Fully differentiated cells with long neurites presented a complete repertoire of ionic channels: voltage dependent Na+ and Ca2+ channels, Ca2+ activated K+ channel and K+ delayed rectifier.

Animals↗
PubMed1984

Postsynaptic acetylcholine receptor efficacy is similarly increased by detergents and acetylcholinesterase inhibitors at an Aplysia synapse.

At Aplysia H- and D-type cholinergic neuro-neuronal synapses, application of high concentrations of detergents (Triton X-100 and sodium deoxycholate) depressed synaptic transmission and the postsynaptic response to ionophoretic application of acetylcholine (ACh) or carbachol. However, when very low concentrations of detergents (of the order of 10(-9) M for sodium deoxycholate) were used, the nerve-evoked response as well as the ACh and carbachol ionophoretic responses were facilitated (by at least 200%), but only in H-type cells. This facilitation was similar to that previously observed in the same receptor type when acetylcholinesterase (AChE) was inhibited by various organophosphate or carbamate acetylcholinesterase inhibitors (AChEIs)3. Indeed, the effects of AChEI and detergents were not cumulative. We propose that on H-type synapses detergents may perturb a hypothetical molecular interaction between AChE and the acetylcholine receptor (AChR) by which AChE modulates the ability of the AChR to be activated by ACh or carbachol.

Acetylcholine↗
PubMed1983

Possible role of acetylcholinesterase in regulation of postsynaptic receptor efficacy at a central inhibitory synapse of Aplysia.

Most of the effects of acetylcholinesterase (AChE) on synaptic transmission are considered to be related to its acetylcholine (ACh) hydrolysing properties. This is clearly apparent from changes which occur in the characteristics of the miniature endplate potential and of the endplate potential at neuromuscular junctions when AChE is inhibited1-4 and during the development of enzymatic AChE activity at maturing synapses5. However, we report here that after inhibiting AChE in a cholinergic synapse in Aplysia, we found an increase not only in postsynaptic responses to presynaptic stimulation and to ionophoretic application of ACh on postsynaptic receptors, but also to ionophoretic application of carbachol. This could not be explained by the inhibition of the ACh hydrolysing function of the enzyme, as carbachol is not hydrolysed by AChE. A possible explanation of these observations is that inhibition of the enzyme affects a property of the ACh receptor (AChR) itself.

Acetylcholinesterase↗
PubMed1983

Side effects of phosphorylated acetylcholinesterase reactivators on neuronal membrane and synaptic transmission.

The side effects of four phosphorylated cholinesterase reactivators (oximes): contrathion, TMB4, toxogonine and 1574 SEBC on membrane properties and synaptic transmission of Aplysia central neurons were investigated. Applied in the bath at 10(-3) mol X 1(-1) to 10(-2) mol X 1(-1) concentrations, all these oximes had a depressive action on cholinergic transmission exerting a curare-like effect on the postsynaptic receptors. In addition, Toxogonin and TMB4 affected the presynaptic voltage dependent sodium conductance. None of these oximes interfered with the voltage dependent potassium or calcium conductances. The oximes had a transient facilitatory action on amplitude of the response to ionophoretically applied acetylcholine (ACh) on H-type ACh receptors, but not on cells with D-type ACh receptors. The K+ dependent response to ACh injection on pleural ganglion cells was selectively blocked by 5 X 10(-6) mol X 1(-1) contrathion. All oximes at 10(-2) mol X 1(-1) to 10(-3) mol X 1(-1) similarly depressed serotonin receptors in buccal ganglion cells. All the effects of oximes were reversible by washing. It was concluded that oximes can act as 1) inhibitors of Na+ conductance, 2) antagonists for various synaptic receptors, 3) reversible inhibitors of acetylcholinesterase.

Animals↗
PubMed1983

Direct and indirect effects of an organophosphorus acetylcholinesterase inhibitor and of an oxime on a neuro-neuronal synapse.

The action of an irreversible inhibitor of acetylcholinesterase (AChE), the organophosphorus compound, ecothiopate iodide, and of a reactivator of phosphorylated AChE, contrathion, were analysed on acetylcholine (ACh) receptors and cholinergic synaptic transmission in the buccal ganglion of Aplysia. At high concentration (above 10(-4)mol X 1(-1), both compounds exerted a curare-like depression on ACh receptors which was reversible with washing. Both compounds reversibly facilitated the current response to ionophoretic application of ACh and increased the evoked postsynaptic current (PSC) as well as the miniature postsynaptic currents (MPSCs). All responses also showed an increase in decay time. These modifications, when induced by ecothiopate iodide were irreversible by washing; however they could be reversed if first washed with contrathion. Neither the organophosphate compound or the oxime did change the number of quanta released per impulse. The current response to ionophoretic application of carbachol also increased after ecothiopate iodide was added. In the limits of the method used, the conductance and opening time of postsynaptic ionic channels opened by ACh were not found to be modified by the two compounds. It was concluded that the facilitatory action of the organophosphorus inhibitors cannot be solely explained by the inhibition of ACh hydrolysis.

Acetylcholine↗
PubMed1983

Carbachol can be released at a cholinergic ganglionic synapse as a false transmitter.

Carbachol was injected into a presynaptic cholinergic neuron in the buccal ganglion of Aplysia and the quantal aspects of the Cl- -dependent postsynaptic response to a prolonged stimulation were analyzed by a statistical fluctuation method. The calculated amplitude of the miniature postsynaptic current was increased with respect to control. Statistical fluctuation analysis was also used to analyze the postsynaptic response obtained during ionophoretic application of acetylcholine and carbachol. The calculated unitary channel current was found to be greater for carbachol than for acetylcholine. This increase could explain the larger miniature postsynaptic current seen after intracellular injection of carbachol into the presynaptic neuron if carbachol was released at the synapse as a false transmitter. This conclusion was supported by the observation that it was possible to restore transmission at a synapse previously blocked by presynaptic intracellular injection of acetylcholinesterase with a presynaptic injection of carbachol.

Acetylcholine↗
PubMed1981

Action of colchicine on membrane currents and synaptic transmission in Aplysia ganglion cells.

The action of colchicine, a drug known to disrupt microtubules, on synaptic transmission and voltage-dependent phenomena was studied. Colchicine depressed transmission in both cholinergic and noncholinergic Aplysia ganglionic synapses. In some synapses, this effect was partly due to the curare like properties of the alkaloid. CA2+ currents, analyzed by voltage clamp techniques, were rapidly depressed by intracellular injection of colchicine and more slowly depressed by external application. Injected colchicine acted at much lower concentrations than required extracellularly. The implication of the reduced calcium influx in synaptic transmission is discussed. Colchicine caused a shift in the reversal potential of acetylcholine-activated chloride channels in a direction consistent with an increased intracellular chloride activity. It was concluded that the wide range of actions of colchicine on membrane properties should be taken into account when this drug is used in biological research.

Animals↗
PubMed1980

Quantal release of acetylcholine examined by current fluctuation analysis at an identified neuro-neuronal synapse of Aplysia.

Quantal events have been analyzed at a neuro-neuronal synapse of Aplysia where the nature of the transmitter is established and both presynaptic and postsynaptic neurons are identified and can be voltage-clamped. Prolonged depolarizations were applied to the presynaptic neuron, which gave rise in the postsynaptic cell to a current response characterized by current fluctuations or noise. Acetylcholine was also applied ionophoretically on the same postsynaptic cell. Amplitude and time course of miniature currents and acetylcholine-activated chloride channels of the same cell were examined by using a current fluctuation analysis. It was estimated that one presynaptic spike releases about 180 quanta, each opening 500 chloride channels.

Acetylcholine↗
PubMed1980

Sialic acid containing substrates as intracellular calcium receptors involved in transmitter release.

The possible function of sialic acid containing substrates in the synaptic terminals was studied by intracellular injection of ruthenium red (RuR) and neuraminidase (NAA). When injected into cholinergic and non cholinergic neurons of Aplysia, NAA and RuR, known to have similar molecular targets, blocked synaptic transmission. The subcellular sites of action of these molecules were investigated. 1. ACh receptors are not affected by RuR. 2. An intracellular site of action of RuR is likely, as less was necessary to block transmission when injected into the presynaptic cell than when applied in the bath. 3. Ca++ channels are not blocked by RuR or neuraminidase. 4. Transmission block is not due to an axonal conduction block, since strong somatic depolarization is not able to induce transmitter release in the presence of RuR. 5. Biochemical analysis of pools of 3H ACh was performed in controls and after injection of RuR. RuR appeared to significantly increase the cytoplasmic ACh pool without any change of the vesicular ACh pool. 6. Quantal release of transmitter was analysed with a current fluctuation method. There were no changes in the amplitude or decay time (tau) of miniataure postsynaptic potentials, but a decrease in the quantal content of the synapse was found.

Animals↗
PubMed1979

Transmitter release: ruthenium red used to demonstrate a possible role of sialic acid containing substrates.

1. The possible function of sialic acid-containing substrates (SACS) in synaptic terminals of Aplysia was studied by intracellular injection of ruthenium red and of neuraminidase. 2. Ruthenium red, a dye known to have sialic acid as a molecular target, blocked transmission irreversibly in both cholinergic (buccal ganglion) and non-cholinergic (cerebral ganglion) synapses. 3. An intracellular site of action is likely because much less ruthenium red was necessary to block transmission when it was injected intracellularly than when it was presented by bath perfusion. 4. Ca2+ spikes recorded in the presence of tetrodotoxin or in Na+-free solution were not modified by ruthenium red or neuraminidase injections or perfusions. It is therefore improbable that these substances blocked transmission by blocking voltage-dependent Ca2+ influx. 5. Strong electrotonic depolarization of a pre-synaptic interneurone in the presence of 10(-4) M-tetrodotoxin caused a sustained post-synaptic response, which was abolished by ruthenium red. This result eliminates axonal conduction block as the principal mechanism of ruthenium red action. 6. Post-synaptic responses to ionophoretically applied acetylcholine (ACh) were not modified by bath perfusion of 2 x 10(-2) M-ruthenium red. 7. Biochemical analysis of pools of [3H]ACh was performed after injection of a precursor, [3H]acetate, into an identified interneurone. Ruthenium red appeared to increase significantly the 'free' (cytoplasmic) ACh pool without any change of 'bound' (vesicular) [3H]ACh-pool. 8. A model is proposed in which SACS act as intracellular Ca2+ receptors involved in transmitter release.

Action Potentials↗
PubMed1978

Uncoupling of electrotonic synapses by calcium.

The degree of axo-axonal synaptic coupling between nerve cells in the buccal ganglion of Navanax was investigated in relation to intracellular ionic calcium. Increasing intracellular Ca2+ by injection of Ca2+, injection of Na+, or application of ionophore X537A produced uncoupling after at least 90 min, if metabolic inhibitor was present in the medium. Subsequent removal of the metabolic inhibitor reestablished the coupling in less than 30 min. Injected Sr2+ also mimicked the uncoupling action of Ca2+. The presence of a metabolic inhibitor alone had no effect on the coupling. These results lead to the following conclusions: (i) Uncoupling is due to an increased free Ca2+ concentration at the junctions. (ii) The liberation of endogenous sequestered Ca2+ is not sufficient to produce uncoupling except if an excess Ca2+ had been previously sequestered. The electrical synapses in the buccal ganglion of Navanax thus appear to be affected by Ca2+ in a similar way as gap junctions studied in non-neural tissues.

Animals↗
PubMed1978

The role of cyclic AMP in the modulation of synaptic efficacy.

1. Heterosynaptic facilitation (modification of synaptic transmission by a neuron influencing the terminals of the presynaptic neuron) was studied in the pleural ganglion of Aplysia. Among several identified synapses, heterosynaptic facilitation was observed only in one type (EIPSP synapses) when repetitive stimulation was applied to the tentacular nerve or to a particular identified neuron. 2. Serotonin was shown to increase the amplitude of the EIPSP at this synapse; this facilitatory effect was prolonged in the presence of theophylline and mimicked by cyclic AMP. 3. When transmission was abolished by calcium-free solution, calcium injected in the region of the synapse caused partial recovery of the EIPSP; when calcium injection was preceded by serotonin injection near the same terminal, the EIPSP was much larger than with calcium injection alone. 4. It was concluded that the activation of one neuron (the heterosynaptic neuron) caused it to release serotonin, which activated an adenylate cyclase in the pre-synaptic terminals of another neuron. Consequent accumulation of cyclic AMP in these terminals is supposed to have increased their voltage-dependent calcium conductance and hence the amount of transmitter released during an action potential.

Animals↗