Biomedical subjects

E Cherubini

Publications and source records attributed to E Cherubini.

At least 91 records · Page 5Linked to original sources

PubMed1990

The allosteric glycine site of the N-methyl-D-aspartate receptor modulates GABAergic-mediated synaptic events in neonatal rat CA3 hippocampal neurons.

We report in this study that, in the presence of magnesium, bath application of micromolar concentrations of glycine have prominent effects on synaptic events and N-methyl-D-aspartate (NMDA) responses in neonatal but not in adult hippocampal slices. Intracellular recordings were made from 71 rat CA3 hippocampal neurons in neonatal slices. In keeping with our earlier study, during the first postnatal week, CA3 neurons exhibited giant depolarizing potentials (GDPs). These GDPs are mediated by gamma-aminobutyric acid (GABA) acting on type A GABA (GABAA) receptors and modulated presynaptically by NMDA receptors. In the majority of cells (18 out of 31), glycine (10-30 microM) increased the frequency of GDPs (from 0.14 to 0.29 Hz). This effect was mimicked by D-serine (10-20 microM) and blocked by the NMDA receptor antagonists D-(-)-2-amino-5-phosphonovalerate (50 microM) and DL-2-amino-7-phosphonoheptanoate (50 microM) and by the GABAA antagonist bicuculline (10 microM) but not by strychnine (1 microM). Subthreshold concentrations of glycine (or D-serine) and NMDA, when given together, enhanced synaptic noise and the frequency of GDPs. In the presence of tetrodotoxin (1 microM), glycine and D-serine (up to 50 microM) did not modify the NMDA-induced inward currents in CA3 pyramidal cells. However the reduction of NMDA-mediated currents by 7-chlorokynurenate (10-20 microM) was reversed by glycine and D-serine (100-200 microM). In contrast, glycine (up to 100 microM) had no effect on membrane potential, input resistance, or NMDA responses after postnatal day 10. It is concluded that GABA-mediated events are facilitated by glycine acting on presynaptically located NMDA receptors.

Aging↗

PubMed1990

Cation current activated by hyperpolarization in a subset of rat nucleus accumbens neurons.

1. Intracellular recordings were made from neurons in slices of rat nucleus accumbens in vitro. Membrane currents were measured in the potential range -60 to -120 mV with the use of a single-electrode, voltage-clamp amplifier. 2. A minority of neurons (28/285) was identified that had resting membrane potentials almost 20 mV less negative than the majority of the cells. These cells, but not the majority, had an inward current that activated slowly when the cells were hyperpolarized from -60 to -120 mV. The time constant of activation was approximately 3 s at -70 mV and 100 ms at -120 mV. 3. This inward current was completely blocked by external cesium (2 mM) but unaffected by barium. The current was reduced in solutions containing low-sodium concentration and increased in solutions with high-potassium concentration; its reversal potential was estimated to be -36 mV. 4. It is concluded that two types of neuron can be distinguished in the rat nucleus accumbens on the basis of the presence or absence of a cation current activated by hyperpolarization. This current (IH, also called If and IQ) causes the neurons to have less-polarized resting potentials than the majority of nucleus accumbens neurons.

Animals↗

PubMed1989

N-methyl-D-aspartate induces recurrent synchronized burst activity in immature hippocampal CA3 neurones in vitro.

Slices of hippocampus prepared from rats aged 1-10 days have been used to examine the chemosensitivity of CA3 pyramidal neurones to N-methyl-D-aspartate (NMDA). Superfusion of NMDA excited all neurones tested at all ages including the first day postnatal. In the majority of neurones this excitation was associated with the induction of a period of burst firing which disappeared on removal of NMDA. These bursts took the form of paroxysmal depolarizing shifts (PDSs) with a large amplitude depolarization and a high frequency discharge of spikes. The amplitude but not the frequency of occurrence of the PDSs was influenced by changes in the membrane potential and they could be abolished by either a high divalent cation medium or tetrodotoxin. Their occurrence was synchronous with an extracellularly recorded discharge. The NMDA induced excitation and the induction of the PDSs was attenuated by selective NMDA receptor antagonists D-aminophosphonovalerate (10-50 microM) and D,L-aminophosphonoheptanoate (20-30 microM). The results indicate that chemosensitivity to NMDA develops prenatally and that activation of NMDA receptors can in immature CA3 pyramidals induce recurrent synchronized burst activity.

2-Amino-5-phosphonovalerate↗

PubMed1989

Endogenous and network bursts induced by N-methyl-D-aspartate and magnesium free medium in the CA3 region of the hippocampal slice.

The epileptogenic properties of N-methyl-D-aspartate and magnesium-free medium were investigated in the CA3 region of the hippocampal slice preparation in the rat. Bath application of N-methyl-D-aspartate (5-10 microM) or magnesium-free medium induced both spontaneous and stimulus-evoked bursts. Both endogenous and network bursts were generated, the former always preceding the latter. The paroxysmal depolarizing shift underlying the network bursts generated by N-methyl-D-aspartate and magnesium-free medium resembled a giant excitatory postsynaptic potential with a reversal potential near 0 mV and a synaptic input in the apical dendrites above the mossy fibre zone. In the presence of N-methyl-D-aspartate or magnesium-free medium, population bursts were synchronized by activating single CA3 neurons. N-methyl-D-aspartate receptor antagonists prevented the development of N-methyl-D-aspartate-induced spontaneous and stimulus-evoked bursts. However, the only N-methyl-D-aspartate receptor antagonist effective in preventing such bursts in magnesium-free medium was DL-3-[(+/-)-2-carboxypiperazin-4-yl-]-propyl-1-phosphonic acid. Endogenous bursting in the CA3 region has not been observed with other convulsants and thus may reflect the novel voltage dependence of the N-methyl-D-aspartate receptor gated ionic channel. N-methyl-D-aspartate receptors may also partially contribute to the excitatory interaction between CA3 neurons and thereby account for the synchronization of the population observed when activating single CA3 neurons.

Animals↗

PubMed1989

Mechanism of induction of long term potentiation by the mast cell degranulating peptide.

The properties of Long Term Potentiation (LTP), which is a sustained enhancement of the synaptic response produced by a brief train of electrical stimulation, and its mechanisms are briefly reviewed. Bath application of the mast cell degranulating peptide (MCD) - a peptide isolated from bee venom- also produces in hippocampal slices LTP which is indistinguishable from that produced by a train of electrical stimulation (no change in postsynaptic cell properties, APV sensitive). In vivo push-pull experiments indicate that this LTP is not associated with a sustained enhancement of release of glutamate and aspartate, the two principle transmitters of the hippocampus, but there is a delayed enhanced release of proteins in the extracellular space which may contribute to the maintenance of the potentiation.

Electric Stimulation↗

PubMed1989

Giant synaptic potentials in immature rat CA3 hippocampal neurones.

1. Intracellular recordings were made from rat CA3 hippocampal neurones in vitro during the first eighteen days of postnatal life. The cells had resting membrane potentials more negative than -51 mV, action potentials greater than 55 mV and membrane input resistances of 117 +/- 12 M omega. An unusual characteristic of these cells was the presence of spontaneous giant depolarizing potentials (GDPs) which were observed during the first eight postnatal (P) days in over 85% of neurones. They were less frequent between P9 and P12 (48%) and disappeared after P12. 2. The GDPs were synchronously generated by a population of neurones; they reversed polarity at -27 mV when recorded with KCl-containing electrodes and at -51 mV with potassium acetate- or potassium methylsulphate-filled electrodes. 3. The GDPs were blocked by bath application of bicuculline (10 microM) or picrotoxin (100-200 microM). Exogenously applied gamma-aminobutyric acid (GABA; 0.2-1 mM) induced at resting membrane potential a bicuculline-sensitive membrane depolarization which reversed polarity at -25 and -51 mV when recorded with KCl- or potassium methylsulphate-filled electrodes respectively. 4. The GDPs were reduced in frequency or blocked by the N-methyl-D-aspartate (NMDA) receptor antagonists DL-2-amino-7-phosphonoheptanoate (AP-7; 50 microM), D(-)2-amino-5-phosphonovalerate (AP-5, 10-50 microM) and (+-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10-50 microM) or NMDA channel blockers phencyclidine (2 microM) and ketamine (20 microM). 5. Stimulation of the hilus during the first week of life evoked a GDP followed by a hyperpolarization. The GDPs were generated by a population of synchronized neurones and reversed polarity at -27 mV with KCl-filled electrodes and at -52 mV with potassium acetate- or potassium methylsulphate-containing electrodes. 6. Bath application of bicuculline (1-10 microM) or picrotoxin (100-200 microM) reversibly blocked the evoked GDPs in the majority of cells. The NMDA receptor antagonists AP-5 (50 microM), AP-7 (50 microM) and CPP (30 microM) usually reduced the amplitude and the duration of the evoked GDPs. In neurones in which evoked GDPs were blocked by bicuculline, a NMDA-mediated component was revealed by increasing the strength or the frequency of stimulation. 7. During the second week of postnatal life, when spontaneous GDPs were extremely rare or absent, superfusion with bicuculline (10 microM) induced, as in adult slices, interictal discharges. These reversed polarity near 0 mV with KCl- or potassium acetate-containing electrodes and were reduced in amplitude and duration by AP-5 (50 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1989

Anoxia produces smaller changes in synaptic transmission, membrane potential, and input resistance in immature rat hippocampus.

1. The reversible blocking effect of brief anoxia (2-4 min) on synaptic transmission was studied in submerged hippocampal slices (kept mostly at 34 degrees), obtained from adult (greater than 120 g) and very young (6-50 g) Wistar rats. Excitatory postsynaptic potentials (EPSPs) were recorded with extra- and intracellular electrodes, sometimes simultaneously: in CA1, they were evoked by stratum radiation stimulation, in CA3 by hilar stimulation. 2. In slices from adults, EPSPs in CA1 were depressed by 90% after 2 min of anoxia, and postanoxic recovery was relatively slow (one-half recovery times 4.0 +/- 0.23 min, mean +/- SE). EPSPs in CA3 were consistently more resistant, especially those generated by mossy fibers; after 2 min of anoxia, these were reduced by only 14.7 +/- 5.4%. 3. In newborn animals (PN1-4), both intra- and extracellular EPSPs (but no population spikes) could be recorded in CA1. Although smaller and more fatigable than in the adult, they were much more resistant to anoxia, after 2 min being reduced by only 44.1 +/- 8.8%; and they were not abolished even after 6-7 min. On the other hand, postanoxic recovery was very rapid, being one-half complete in 2.4 +/- 0.48 min. Only large and very prolonged (giant) depolarizing PSPs [probably inhibitory postsynaptic potentials (IPSPs)] could be recorded in CA3 neurons; they were rapidly blocked by anoxia. 4. In older pups (PN6-21), the CA1 EPSPs became progressively more sensitive to anoxia. At the end of the second week, they were as rapidly blocked as in slices from adults; but postanoxic recovery remained quicker throughout this period. In CA3, EPSPs could now be evoked that were as resistant to anoxia as in adult slices. 5. In both CA1 and CA3 neurons from adult rats, anoxia (for 2-3 min) reduced the input resistance (RN) by 45.7 +/- 6.25%. In CA1 neurons, there was most often some hyperpolarization (-7.2 +/- 1.8 mV), which was less consistent in CA3 cells. The return of O2 typically led to a second (postanoxic) phase of hyperpolarization (-7.9 +/- 1.93 mV). 6. At PN1-4, the resting potential (Vm) of most cells had to be maintained by current injection; the input resistance (RN) of CA1 neurons was 70% higher than in mature cells, and there was little time-dependent inward rectification. Anoxia produced no regular changes in Vm, and reductions in RN were very small (by only 9.6 +/- 5.0%). A postanoxic hyperpolarization was seen in only 2 neurons out of 11.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1989

Anoxia on slow inward currents of immature hippocampal neurons.

1. The effects of brief anoxia (2-4 min) on membrane currents--especially the tetrodotoxin (TTX)-insensitive, Cd2+-sensitive slow inward currents, presumed to be Ca2+ currents--were studied by single-electrode voltage clamp in CA1 and CA3 neurons in submerged hippocampal slices from adult and newborn Wistar rats (PN1-13). 2. In mature neurons, anoxia had no effect on Q-type inward relaxations, but slowly activating C-type outward currents were depressed. The most striking change was the suppression of Ca inward currents (especially the slowly inactivating L-type, by greater than 95%). This effect of anoxia was not sensitive to the N-methyl-D-aspartate (NMDA) receptor blocker, D-aminophosphonovalerate. Anoxia also reversibly abolished the NMDA-evoked inward current. 3. In neurons from newborn animals (PN1-6), Q-type inward relaxations and postanoxic outward currents were very small or undetectable. The slow inward (Ca) currents were smaller than in mature cells, but they showed a clearer separation between low-threshold, fast-inactivating and high-threshold, slowly inactivating currents. Both types of current were more resistant to anoxia (mean depression of L-type was by only 53.3 +/- 5.6%, mean +/- SE). 4. In such immature neurons, the NMDA-evoked inward currents were also more resistant to anoxia. 5. By PN7-13, increasing maturation was reflected in 1) larger voltage-dependent inward currents, 2) increasingly evident Q-type relaxations and postanoxic outward currents, and 3) near-complete blockade of inward currents by anoxia (at PN11-13, mean depression of L-type currents was by 98.5 +/- 1.5%).

Aging↗

PubMed1989

Inward rectification in rat nucleus accumbens neurons.

1. Intracellular recordings were made from neurons in slices cut from the rat nucleus accumbens septi. Membrane currents were measured with a single-electrode voltage-clamp amplifier in the potential range -50 to -140 mV. 2. In control conditions (2.5 mM potassium), the resting membrane potential of the neurons was -83.4 +/- 1.1 (SE) mV (n = 157). Steady state membrane conductance was voltage dependent, being 34.8 +/- 1.7 nS (n = 25) at -100 mV and 8.0 +/- 0.7 nS (n = 25) at -60 mV. 3. Barium (1 microM) markedly reduced the inward rectification and caused a small inward current (40.6 +/- 8.7 pA, n = 8) at the resting potential. These effects became larger with higher barium concentrations, and, in 100 microM barium, the current-voltage relation was straight. 4. The block of the inward current by barium (at -130 mV) occurred with an exponential time course; the time constant was approximately 1 s at 1 microM barium and less than 90 ms with 100 microM. Strontium had effects similar to those of barium, but 1000-fold higher concentrations were required. Cesium chloride (2 mM) and rubidium chloride (2 mM) also blocked the inward rectification; their action reached steady state within 50 ms. 5. It is concluded that the nucleus accumbens neurons have a potassium conductance with many features of a typical inward rectifier and that this contributes to the potassium conductance at the resting potential.

Animals↗

PubMed1988

Antagonism of spontaneous and evoked bursts by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the CA3 region of the in vitro hippocampus.

Superfusion of hippocampal slices with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) antagonized kainate-induced bursts and bursts of unknown origin in the CA3 region. CNQX also increased the latency of and eventually blocked evoked bursts which persist following kainate washout. In contrast, D-(-)-2-amino-7-phosphonoheptanoic acid did not alter burst latency or block bursts unless applied subsequent to CNQX. We conclude that the quisqualate type receptor has a prominent role in burst generation with a smaller contribution from N-methyl-D-aspartate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1988

Changes in voltage dependence of NMDA currents during development.

N-Methyl-D-aspartate (NMDA), applied by superfusion to hippocampal slices evokes comparable peak inward currents in CA3 pyramidal cells of adult and 0-10 day-old rats. However, NMDA current-voltage plots from immature neurones do not consistently show the region of negative slope conductance characteristic of adult. Therefore at a critical stage of development, NMDA activation may elicit substantial inward currents and Ca2+ influx at resting membrane potential.

Aging↗

PubMed1988

Blockade of excitatory synaptic transmission by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the hippocampus in vitro.

Superfusion of hippocampal slices with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 2-5 microM) reversibly blocked the Schaffer collateral and mossy fibre excitatory postsynaptic potential (EPSP), while sparing the fast and slow gamma-aminobutyric acid (GABA)-mediated inhibition. Membrane potential, input resistance and spike accommodation were not altered. Inward currents induced by quisqualate were reduced to a greater extent by CNQX than those induced by kainate or N-methyl-D-aspartate. We suggest that CNQX may be a useful antagonist to study excitatory amino acid-mediated synaptic transmission.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1988

Epileptiform bursts elicited in CA3 hippocampal neurons by a variety of convulsants are not blocked by N-methyl-D-aspartate antagonists.

Intracellular and extracellular recordings from CA3 hippocampal neurons in vitro were used to study the ability of several NMDA (N-methyl-D-aspartate) receptor antagonists to suppress epileptiform bursts induced by NMDA and convulsants not thought to act at NMDA receptors. The antagonists, APV (D-2-amino-5-phosphonovalerate), AP-7 (D,L-2-amino-7-phosphonohepatanoate) and CPP (D,L-3[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid), blocked the spontaneous and evoked bursts induced by NMDA. CPP, but not APV or AP-7, prevented the development of bursts induced by Mg-free medium. The NMDA antagonists failed to block bursting induced by kainate, 7 mM K+, mast cell degranulating peptide, anoxia or spontaneous bursting. In some cases the NMDA antagonists induced spontaneous bursts or enhanced burst frequency, a proconvulsant effect. It is concluded that activation of NMDA receptors is sufficient but not necessary for burst generation in the CA3 region.

2-Amino-5-phosphonovalerate↗

PubMed1988

Brief anoxic episodes induce long-lasting changes in synaptic properties of rat CA3 hippocampal neurons.

The effects of brief anoxic episodes on rat CA3 hippocampal neurons were studied with intracellular and extracellular techniques in the in vitro slice preparation. After repeated (3-7 times), brief (2-6 min duration each) applications of artificial cerebrospinal fluid (ACSF) saturated with 95% N2 and 5% CO2, electrical stimulation of various inputs to CA3 neurons, evoked an excitatory postsynaptic potential (EPSP) followed by an all-or-none burst. This response which persisted for several hours after the last anoxic episode, is reminiscent of the bursts induced by various convulsive agents. Post anoxic bursts are generated by a polysynaptic network which converge on the apical distal segment of CA3 neurons. It is concluded that a repetitive impairement of metabolism produces long lasting changes in the synaptic properties of CA3 neurons.

Action Potentials↗

PubMed1988

Epileptogenic properties of the mast cell degranulating peptide in CA3 hippocampal neurones.

The epileptogenic properties of the mast cell degranulating peptide (MCD) have been investigated in the CA3 region of the hippocampal slice preparation. Brief (3-5 min) bath application of MCD (0.5-2 microM) to CA3 hippocampal neurones produced an enhancement of the spontaneous synaptic activity and the appearance of spontaneous bursts that persisted for several hours. These bursts were network driven and the underlying paroxysmal depolarizing shift met the criteria for a giant excitatory postsynaptic potential (EPSP), with a reversal potential close to 0 mV. Furthermore following the application of MCD, stimulation of the mossy fibres, commissural or temporo-ammonic pathway evoked an EPSP followed by an evoked network burst. The bursts which could be elicited for several hours were reversibly blocked by a brief application of tetrodotoxin (TTX; 1 microM) or cobalt (2 mM). In contrast, prior and concomitant treatment with TTX or cobalt prevented the occurrence of the bursts induced by MCD. The effects of MCD were not due to a blockade of GABAergic inhibition since the toxin did not reduce the fast and slow IPSP. Furthermore, the N-methyl-D-aspartate (NMDA) antagonists D-2-amino-phosphonovalerate (D-APV; 30 microM) or DL-amino-phosphoheptanoic acid (AP-7, 30 microM) did not block the action of MCD, suggesting that the activation of NMDA receptors are neither necessary nor sufficient for MCD-induced bursts. It is concluded that MCD induces in the CA3 region long-lasting changes in the synaptic responses which may be mediated through a presynaptic mechanism.

Action Potentials↗

PubMed1988

Excitatory amino acids in synaptic excitation of rat striatal neurones in vitro.

1. Intracellular recordings were made from rat striatal neurones in vitro. The cells had resting membrane potentials greater than -60 mV and action potentials greater than 70 mV with spike overshoot of 10-30 mV. 2. In the presence of bicuculline intrastriatal stimulation evoked an excitatory postsynaptic potential (EPSP). The relationship between EPSP amplitude and membrane potential was not linear. The EPSP decreased in amplitude and duration for values of membrane potential more negative than -80 mV and increased in amplitude and duration for values of membrane potential more positive than -50 mV. 3. The mean reversal potential for the EPSP recorded with electrodes filled with potassium methyl-sulphate was -9.2 +/- 1.7 mV (mean +/- S.E.M.) in presence of bicuculline (30 microM). A similar reversal potential was obtained with CsCl-filled electrodes. 4. The endogenous broad-spectrum excitatory amino acid antagonist, kynurenic acid (100-500 microM), reduced the EPSP in a dose-dependent way, maximally by 80% at 500 microM, but a residual depolarization remained even at high antagonist concentrations. This effect was associated sometimes with a membrane depolarization and an increase in input resistance. 5. In normal artificial cerebro-spinal fluid solution and at resting membrane potential the specific N-methyl-D-aspartate (NMDA) antagonist, (D,L)-2-amino-7-phosphonoheptanoic acid (([D,L)-AP7), did not affect the EPSP amplitude. However, this antagonist partially reduced the EPSP amplitude when the membrane was depolarized beyond -50 mV by intracellular current injection. 6. The nicotinic cholinergic antagonist mecamylamine (10 microM) caused a partial (24 +/- 3%) reduction of EPSP amplitude at resting potential in normal medium. However, in the cells where a reduction of EPSP amplitude was observed it was always accompanied by membrane depolarization (7.1 +/- 2.1 mV). (+)-Tubocurarine and hexamethonium were without effect at 10 microM. 7. When Mg2+ was removed from the bathing solution, the EPSP increased in amplitude (89 +/- 9.5%) and duration. In Mg2+-free medium at resting membrane potential (D,L)-AP7 (30 microM) partially reduced EPSP amplitudes (59 +/- 2.5%). 8. It is proposed that a major component of the EPSP evoked by intrastriatal stimulation is mediated by excitatory amino acids. At resting membrane potential and in normal medium only non-NMDA receptors seem to contribute to the synaptic depolarization, but at depolarized potentials and in Mg2+-free medium an NMDA receptor-mediated component of the EPSP can be demonstrated.

2-Amino-5-phosphonovalerate↗

PubMed1988

Synaptic potentials in rat locus coeruleus neurones.

1. Intracellular recordings were made from locus coeruleus neurones in a slice of tissue cut from the rat pons. A depolarizing postsynaptic potential (PSP) followed electrical stimulation of the slice surface; the latency was 1-3 ms and the duration was 50-200 ms. 2. The reversal potential of the PSP (estimated by extrapolation from potentials between -60 and -90 mV) was -27 mV when the recording electrodes contained potassium chloride, and -36 mV when electrodes contained potassium acetate or methylsulphate. 3. Kynurenic acid depressed the PSP amplitude by up to 60%. The residual PSP reversed polarity at -50 mV (extrapolated, potassium chloride in electrodes) or -70 mV (observed, potassium methylsulphate in electrodes): it was blocked by bicuculline (10 microM). 4. Exogenously applied gamma-aminobutyric acid (GABA) depolarized cells when the recording electrode contained potassium chloride (reversal potential was -45 mV) and hyperpolarized cells when the recording electrode contained potassium methylsulphate (reversal potential was -70 mV). 5. In the presence of bicuculline, the residual PSP was blocked by kynurenic acid, whereas DL-2-amino-5-phosphonovaleric acid (2-APV) reduced its amplitude to 80% of control. 6. Exogenously applied glutamate, quisqualate and N-methyl-D-aspartate (NMDA) all caused a membrane depolarization (or an inward current under voltage clamp) which reversed polarity at about 0 mV. These effects were blocked by kynurenic acid (500 microM); 2-APV (50 microM) selectively blocked the effect of NMDA. 7. The results indicate that the PSP evoked by focal stimulation within the nucleus locus coeruleus results from an excitatory amino acid acting predominantly at non-NMDA receptors, and from GABA acting at GABAA receptors.

2-Amino-5-phosphonovalerate↗

PubMed1988

Action of naloxone on myenteric neurons removed from morphine-treated guinea pigs.

Guinea pigs were treated chronically with morphine by implantation of pellets and the ileum was later removed for experiments in vitro. Intracellular recording from myenteric neurons showed that chronic morphine treatment led to the development of an increased calcium-dependent afterhyperpolarization, whether this followed an action potential or the depolarization resulting from activation of nicotinic acetylcholine receptors. The properties of the neurons were otherwise normal. Naloxone depolarized about one-third of neurons and led to the appearance of spontaneous fast excitatory postsynaptic potentials in many cells. Extracellular recordings from neurons induced to fire with suction electrodes showed that the excitation caused by naloxone was prevented in solutions that contained sufficient cobalt to block synaptic transmission. Measurements of longitudinal muscle tension of intact pieces of ileum showed that the contracture caused by naloxone was much reduced by prior exposure of the ileum in vitro for 30 min to beta-funaltrexamine. The beta-funaltrexamine appeared to have irreversibly blocked a significant fraction of the mu receptors because the effectiveness of Tyr-D-Ala-Gly-MePhe-Gly-ol to inhibit nerve-evoked contractile responses (twitches) was much reduced in tissues treated with beta-funaltrexamine. These results indicate that at least a portion of the contracture results from an action of naloxone at kappa rather than mu receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗