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Biomedical subjects

E Cherubini

Publications and source records attributed to E Cherubini.

At least 109 records · Page 6Linked to original sources
PubMed1987

Is activation of N-methyl-D-aspartate receptor gated channels sufficient to induce long term potentiation?

Superfusion of hippocampal slices with Mg2+ free medium (20-30 min) produced in CA1 interictal bursts and an enhancement of the Schaffer collateral synaptic response which persisted for over 2 h after return to control media. This long lasting effect, which was blocked by N-methyl-D-aspartate (NMDA) antagonists, was not associated with changes in postsynaptic cell excitability. A cut between CA3 and CA1, which blocked the bursts in CA1 (but not in CA3), also abolished the long lasting effects of Mg2+ free medium. It is concluded that the activation of NMDA receptors gated ionic channels is insufficient per se to induce a long term potentiation of synaptic transmission.

Action Potentials↗
PubMed1987

A ouabain-sensitive hyperpolarization in rat striatal neurones in vitro.

Intracellular recordings were made from rat striatal neurones in vitro. In the presence of intracellular caesium and extracellular tetraethylammonium chloride (TEA) (5 mM) and barium (3 mM), long-lasting plateau potentials developed followed by a prominent voltage independent hyperpolarization which lasted several seconds. A similar afterhyperpolarization was observed when calcium was replaced by barium. The afterhyperpolarization was reduced in a potassium free medium and reversibly abolished in a Na+-free solution or by cooling the slice to 21-24 degrees C. It was also irreversibly blocked by ouabain (50 microM). This hyperpolarization may therefore result from the activation of a Na+,K+-ATPase electrogenic pump.

Action Potentials↗
PubMed1987

A study of amino acid-activated currents recorded from frog motoneurones in vitro.

Superfusion of the excitatory amino acids glutamate (1-2 mM), quisqualate (15-30 microM) and N-methyl-D-aspartate (NMDA: 15-30 microM) induced inward currents in voltage-clamped motoneurones, in vitro. Typically the NMDA and quisqualate currents had prolonged time courses relative to glutamate currents. No desensitization was apparent during repeated agonist application. D-2-Amino-5-phosphonovalerate (10 microM) selectively antagonized the NMDA current without affecting the quisqualate current; the glutamate current was partially reduced reflecting its mixed agonist properties.

2-Amino-5-phosphonovalerate↗
PubMed1987

An inward calcium current underlying regenerative calcium potentials in rat striatal neurons in vitro enhanced by Bay K 8644.

The single electrode voltage clamp technique was used to characterize the currents underlying the calcium potentials in rat caudate neurons in vitro. In current clamp experiments, long depolarizing current pulses evoked repetitive firing of fast somatic action potentials. These were abolished by tetrodotoxin (1 microM) and replaced by slow graded depolarizing potentials. These were preceded by a transient hyperpolarizing notch. Addition of 4-aminopyridine (100 microM) abolished the hyperpolarizing notch, enhanced the slow graded depolarizing response and induced the appearance of a slow all-or-nothing action potential. Both the slow graded response and the all-or-nothing action potential were abolished by cobalt (2 mM), suggesting the involvement of voltage-dependent calcium conductances. When the neurons were loaded intracellularly with caesium the action potential duration increased. Substitution of the extracellular calcium by barium (1-3 mM) or external addition of tetraethylammonium (5 mM) further prolonged spike duration and induced the appearance of long-lasting plateau potentials. These were insensitive to tetrodotoxin and were reversibly blocked by the calcium antagonists cobalt (2 mM), manganese (2 mM) or cadmium (500 microM). The calcium potentials were enhanced by the calcium 'agonist' BAY K 8644 (1-5 microM). In voltage clamp experiments when intracellular caesium was used to reduce outward currents and tetrodotoxin to block fast regenerative sodium currents, depolarizing voltage steps from a holding potential of -50, -40 mV activated an inward current. This current peaked in 50-80 ms and inactivated in two phases: an initial one at 150-200 ms followed by a second one after several hundred ms.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Kainate reduces two voltage-dependent potassium conductances in rat hippocampal neurons in vitro.

The mechanisms of action of kainate were studied in CA1 hippocampal neurons using the single electrode voltage-clamp technique in vitro. Kainate (100-200 nM) reduced the potassium current which is responsible for the anomalous rectification (IQ). In 30% of the cells the drug reduced the calcium-dependent potassium current (IC) which is responsible for the afterhyperpolarization that follows calcium action potentials. The reduction of IC will contribute to the enhancement of the neural excitability by this drug.

Action Potentials↗
PubMed1985

Benzodiazepines both enhance gamma-aminobutyrate responses and decrease calcium action potentials in guinea-pig myenteric neurones.

The effect of two benzodiazepines, midazolam and diazepam, was studied in guinea-pig myenteric neurones, using intracellular recording techniques. Both these benzodiazepines (100-300 pM) potentiated the rapidly desensitizing, bicuculline-sensitive depolarization, induced by alpha-aminobutyrate ionophoresis. Concentrations of midazolam and diazepam higher than 100 nM depressed the gamma-aminobutyrate-induced depolarization. The potentiating effect of the benzodiazepines was reversibly abolished by Ro 15-1788 (1-100 nM) and by pentylenetetrazol (100 microM). A second effect of midazolam and diazepam (100-300 pM) was a reversible depression of the amplitude and duration of the directly evoked action potential in 29% of neurones, without affecting membrane potential or conductance. The effect was very marked when electrodes were filled with CsCl, and was also seen in the presence of tetrodotoxin. In some but not all of these neurones, the amplitude and duration of the action potentials was reduced also by gamma-aminobutyrate (1-10 microM). Ro 15-1788 and pentylenetetrazol reversibly abolished the effect of benzodiazepines on the action potential, but not that of gamma-aminobutyrate. Thus, benzodiazepines have two effects on myenteric neurones. The first is an enhancement of the gamma-aminobutyrate response (activation of Cl conductance); the second is a depression of the calcium action potential, which appears to be independent of gamma-aminobutyrate.

Action Potentials↗
PubMed1985

Mu and kappa opioids inhibit transmitter release by different mechanisms.

The actions of various opioids were examined on calcium action potentials in the cell somata of guinea pig myenteric neurones and on the release of acetylcholine at synapses onto these cells. The opioids morphine, normorphine, and [D-Ala2, MePhe4, Met5(O)]enkephalin-ol caused membrane hyperpolarizations resulting from an increase in potassium conductance; opioids that are more selective agonists for the kappa receptor subtype (dynorphin, tifluadom, U50488H) did not. Conversely, calcium action potentials were depressed or abolished by the kappa opioids but were not affected by morphine and [D-Ala2, MePhe4, Met(O)5]enkephalin-ol. Both groups of opioids caused presynaptic inhibition of acetylcholine release in the myenteric plexus, depressing the amplitude of the fast excitatory postsynaptic potential. The presynaptic inhibition caused by [D-Ala2, MePhe4, Met(O)5]enkephalin-ol, morphine, and normorphine, but not that caused by the kappa opioids, was prevented by pretreatment with the selective mu site-directed irreversible antagonist beta-funaltrexamine. Furthermore, the presynaptic inhibitory action of morphine and [D-Ala2, MePhe4, Met(O)5]enkephalin-ol, but not that of the kappa-receptor agonists, was reversibly blocked by barium. The results suggest that presynaptic inhibition caused by mu receptor activation probably results from an increase in potassium conductance, whereas kappa-receptor agonists may depress the release of acetylcholine by directly reducing calcium entry into the nerve terminals.

Acetylcholine↗
PubMed1985

Opioid inhibition of synaptic transmission in the guinea-pig myenteric plexus.

Intracellular recordings were made from neurones in the myenteric plexus of the guinea-pig ileum. Presynaptic nerves were excited by a focal stimulating electrode on an interganglionic strand. Fast excitatory postsynaptic potentials (e.p.s.ps) were depressed in amplitude by morphine and [Met5]enkephalin in the concentration range of 1 nM-1 microM. Nicotinic depolarizations evoked by exogenously applied acetylcholine (ACh) were not affected by these opioids. Hyperpolarization of the presynaptic fibres probably contributed to the depression of the fast e.p.s.p. because fast e.p.s.ps evoked by low stimulus voltages were more depressed than those evoked by high stimulus voltages and fast e.p.s.ps resulting from activation of a single presynaptic fibre were blocked in a non-graded manner. Opioids depressed the slow e.p.s.p. in those neurones in which they did not change the resting membrane potential. The slow e.p.s.p. was increased in amplitude in those neurones hyperpolarized by opioids. Depolarizations resulting from application of barium, substance P or ACh were also enhanced by opioids. Equivalent circuit models in which opioids increase, and substance P or ACh decrease, the same potassium conductance could account for this enhancement. The actions of opioids were prevented or reversed by naloxone (1 nM-1 microM). It is concluded that morphine and enkephalin inhibit the release of ACh and a non-cholinergic transmitter from fibres of the myenteric plexus, and that this may involve a hyperpolarization of presynaptic fibres. Additionally, opioids can interact postsynaptically with other substances which affect membrane potassium conductances.

Acetylcholine↗
PubMed1984

Somatic and dendritic actions of gamma-aminobutyric acid agonists and uptake blockers in the hippocampus in vivo.

In rats under urethane anaesthesia gamma-aminobutyric acid agonists and uptake blockers were microiontophoretically applied in the pyramidal layer of CA1 and in the apical dendrites using a twin set of multibarrelled micropipettes. Thus, the somatic and dendritic field potentials elicited by commissural stimulation were recorded simultaneously and the effects of iontophoretic applications at either site studied. Somatic applications of gamma-aminobutyric acid, isoguvacine or muscimol produced an inhibition of the somatic population spike; this showed rapid fade and was followed by an "off" response i.e. an enhancement of the population spike discharge and the occurrence of a second (and occasionally third) spike. The order of potency with regard to the "off" response was muscimol greater than isoguvacine much greater than gamma-aminobutyric acid. In contrast, the inhibition of the population spike produced by 4,5,6,7-tetrahydroisoxazolo(5,4-C) pyridin 3-OL showed little fade and no prominent "off" response. The fade and "off" response were not associated with significant changes in the dendritic field excitatory postsynaptic potential concommittantly recorded and were exclusively restricted to the immediate vicinity of the pyramidal layer. Ejection of gamma-aminobutyric acid and its agonists in the stratum radiatum produced a reduction of the field excitatory postsynaptic potential and the somatic spike, this effect however showed no fade (even during prolonged applications of high doses) and no "off" response. Somatic applications of the uptake blockers nipecotic acid or guvacine consistently produced: an increase in the effectiveness of the inhibition produced by gamma-aminobutyric acid and its analogues: a decrease in the latency to peak of the inhibition and an increase in the time to recovery; a full blockade of the fade and the "off" response. All of these effects were rapid and fully reversible without significant changes in either the field excitatory postsynaptic potential or the (control) somatic spikes. The more specific glial uptake blocker, 4,5,6,7-tetrahydroisoxazolo(4,5-C) pyridin 3-OL occasionally blocked the "off" response, however it was less potent and also tended to reduce the spike amplitude. Dendritic applications of the uptake blockers reduced the excitatory postsynaptic potential and the somatic spike but failed to produce prominent changes in the action of gamma-aminobutyric acid and its analogues.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1984

Quinine blocks a calcium-activated potassium conductance in mammalian enteric neurones.

Quinine (100 microM) abolished the slow calcium-dependent afterhyperpolarization which occurs after an action potential in some neurones of the guinea-pig myenteric and submucous plexus. This occurred without any effect on the amplitude or time course of the action potential itself, or on the faster calcium-independent afterhyperpolarization. Tetraethylammonium did not reduce the slow afterhyperpolarization. Quinine also abolished the hyperpolarization which was evoked by intracellular injection of calcium ions.

Action Potentials↗
PubMed1984

Morphine augments calcium-dependent potassium conductance in guinea-pig myenteric neurones.

Intracellular recordings were made from myenteric neurones removed from guinea-pig ileum and maintained in vitro. Action potentials were elicited by passing brief depolarizing currents through the recording electrode. In AH cells they were followed by afterhyperpolarizations resulting from an increase in potassium conductance (GK,Ca). Morphine (1 nM - 1 microM), applied by superfusion, increased the duration of the afterhyperpolarization (and the underlying GK,Ca) which followed from 1 to 30 action potentials. Morphine did not change the peak amplitude of the afterhyperpolarization. This action of morphine occurred both in cells which showed no change in resting membrane potential or resistance and in cells which were hyperpolarized. It was prevented by naloxone (10 nM - 1 microM). The possibility is proposed that morphine inhibits one of the mechanisms by which myenteric neurones control their free intracellular calcium concentration close to the plasma membrane.

Action Potentials↗
PubMed1984

Actions of gamma-aminobutyric acid on neurones of guinea-pig myenteric plexus.

The effects of gamma-aminobutyric acid (GABA) applied by ionophoresis, pressure ejection and superfusion to myenteric neurones of the guinea-pig ileum were investigated by intracellular recording techniques. Ionophoretic or pressure application of GABA (10 pC-30 nC) caused membrane depolarizations of AH neurones but not S neurones. This depolarization was associated with a conductance increase. It reversed polarity at a membrane potential of -18 mV when intracellular electrodes contained KCl, and -39 mV when electrodes contained K acetate, citrate or sulphate. The ionophoretic depolarization was antagonized by bicuculline (1-30 microM) in an apparently competitive manner. During prolonged or repeated ionophoretic application of GABA, both the depolarization and conductance increase desensitized. Superfusion of GABA (1-100 microM) caused a membrane depolarization in AH neurones, associated with an increase in membrane conductance. The increase in conductance was always smaller than that evoked by ionophoresis of GABA. Bicuculline only partially depressed the depolarization induced by superfusion of GABA, particularly slowing its rising phase. beta-p-Chlorophenyl GABA (baclofen) (10 microM) caused a depolarization similar to that observed with GABA in the presence of bicuculline. The depolarization induced by baclofen and GABA (in presence of bicuculline) superfusion did not decline during prolonged applications; superfusion of GABA but not baclofen reversibly reduced or eliminated the effects of GABA ionophoresis. It is concluded that GABA has two effects on the membrane of myenteric neurones. The first is a bicuculline-sensitive, rapidly desensitizing chloride activation: the second is a bicuculline-insensitive, non-desensitizing depolarization.

Acetylcholine↗
PubMed1984

Inhibition of calcium spikes and transmitter release by gamma-aminobutyric acid in the guinea-pig myenteric plexus.

The effect of gamma-aminobutyric acid (GABA) (1 microM-1 mM) on synaptic transmission in isolated myenteric ganglia of guinea-pig ileum was investigated with intracellular recording techniques. GABA (up to 1 mM) had no effect on the resting membrane potential and membrane conductance of S neurones. GABA reduced the amplitude of the fast excitatory postsynaptic potential e.p.s.p.) without changing the amplitude of the nicotinic response to ionophoretic application of acetylcholine (ACh). This effect was mimicked by baclofen (10-100 microM) and was not blocked by bicuculline (10 microM). The preparation did not become desensitized during prolonged GABA applications. Cholinergic and non-cholinergic slow e.p.s.ps evoked by single or repetitive presynaptic nerve stimulation were reduced in amplitude by GABA. GABA did not depress muscarinic responses to ionophoretic application of ACh. GABA reduced the duration of the action potential in AH neurones in concentrations that did not affect the membrane potential or conductance. The effect was very marked when electrodes were filled with CsCl, and tetrodotoxin was in the superfusing solution. This effect was also mimicked by baclofen, was insensitive to bicuculline and was not reduced with repeated application or GABA. It is concluded that GABA inhibits release of ACh and the transmitter mediating the slow e.p.s.p. This effect may result from inhibition of an inward calcium current.

Action Potentials↗
PubMed1983

Nicotinic depolarization activates calcium dependent gK in myenteric neurons.

Intracellular recordings were made from S type neurons in the myenteric plexus of the guinea-pig ileum. Acetylcholine (ACh) was applied directly onto the soma membrane by iontophoresis with visual placement of the iontophoretic pipette. Fast nicotinic depolarizations were evoked which were followed by slow muscarinic depolarizations. After application of hyoscine to block the slow muscarinic depolarization, the nicotinic depolarization was found to be followed by a hyperpolarization. This hyperpolarization was several mV in amplitude and 1-5 s in total duration. It disappeared when the preceding nicotinic depolarization was blocked by hexamethonium. The ACh induced by hyperpolarization was due to calcium entry and subsequent opening of potassium channels.

Acetylcholine↗
PubMed1983

Dual cholinergic modulation of hippocampal somatic and dendritic field potentials by the septo-hippocampal pathway.

In rats under urethane anaesthesia, brief tetanic stimulation of the medial septum produces a dual effect upon the field potentials elicited in the ammon's horn by commissural stimulation: a facilitation of the population spike recorded in the pyramidal layer and a depression of the field EPSP recorded in the apical dendrites. Both effects, which are also produced by local application of muscarinic agents, are antagonized by local administration of muscarinic antagonists.

Acetylcholine↗
PubMed1983

Opposite actions of muscarinic and nicotinic agents on hippocampal dendritic negative fields recorded in rats.

In rats under urethane anaesthesia, microiontophoretic application of muscarinic or nicotinic agents, in the pyramidal layer of the hippocampus, enhanced the population spike (s) evoked by fimbrial stimulation. In contrast, muscarinic and nicotinic agents had an opposite action on on the dendritic field potentials, they respectively reduced and enhanced the negative fields (field EPSP) recorded in the apical dendrites. These effects were antagonized by muscarinic and nicotinic antagonists, respectively.

Acetylcholine↗