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Y Grossman

Publications and source records attributed to Y Grossman.

At least 37 records · Page 2Linked to original sources
PubMed1994

Quantal analysis of presynaptic inhibition, low [Ca2+]0, and high pressure interactions at crustacean excitatory synapses.

The cellular mechanisms underlying the effects of high pressure, GABAergic presynaptic inhibition, and low [Ca2+]0 on glutamatergic excitatory synaptic transmission were studied in the opener muscle of the lobster walking leg. Excitatory postsynaptic currents (EPSCs) were recorded with or without prior stimulation of the inhibitor using a loose macropatch clamp technique at atmospheric pressure and at 6.9 MPA helium pressure. High pressure reduced the mean EPSC amplitude and variance, decreased the quantal content (m), but did not affect the quantum current (q). Pressure shifted the median of the amplitude histogram to the left by 1-2 q. Under normal pressure conditions, presynaptic inhibition and low [Ca2+]0 induced similar effects. However, quantal analysis using a binomial frequency distribution model revealed that high pressure and low [Ca2+]0 diminished n (available active zones) and slightly increased p (probability of release), but presynaptic inhibition reduced p and slightly increased n. At high pressure, presynaptic inhibition was reduced, at which time the major contributor to the inhibitory process appeared to be reduction in n and not p. The similarity of the alterations in quantal parameters of release at high pressure, low [Ca2+]0, and in some conditions of presynaptic inhibition is consistent with the hypothesis that pressure reduces Ca2+ inflow into the presynaptic nerve terminals to affect the Ca(2+)-dependent quantal release parameters n and p.

Animals↗
PubMed1994

Block of GABA-transaminase modifies GABAergic transmission at the crayfish synapses.

1. The cytosolic concentration of a neurotransmitter is believed to be an important factor determining its release. The effects of ethanolamine-O-sulfate (EOS), a gamma-aminobutyric acid (GABA)-transaminase blocker, on GABAergic postsynaptic and presynaptic inhibitory neurotransmission were examined in the crayfish opener neuromuscular synapses. 2. Intracellular recordings of evoked excitatory (EPSPs) and inhibitory postsynaptic potentials (IPSPs) as well as loose macropatch clamp measurements of excitatory (EPSCs) and inhibitory postsynaptic currents (IPSCs) were used to evaluate the effects of the drug, which was applied exclusively to the nerve bundle. 3. Under normal conditions, a stimulus train to the inhibitor before the excitor stimulation elicited two phases of inhibition: 1) a large reduction in EPSP amplitude associated with a decrease in its time constant of decay (tau D) at time intervals of 0-15 ms and 2) a moderate decrease in EPSP amplitude with a small change in EPSP tau D at intervals of 15-90 ms. EOS treatment selectively increased the inhibition of phase 2. 4. The muscle membrane electrical parameters and the existing postsynaptic tonic release of GABA were not affected by the drug. 5. EOS did not alter the IPSP's parameters such as amplitude, reversal potential, and conductance. 6. Quantal analysis of single IPSCs revealed no significant changes in the statistical parameters such as quantum size (q), quantal content (m), number of active zones (n), or probability of release (p). 7. Quantal analysis of EPSCs, released after interaction with the inhibitor, did exhibit a large reduction in m without any effect on q. 8. These results demonstrate that EOS has a specific and differential effect on neural transmission in two synapses of the same axon: it increases presynaptic inhibition without significant effect on the postsynaptic inhibitory mechanism.

4-Aminobutyrate Transaminase↗
PubMed1994

Long-term changes in neocortical activity after chemical kindling with systemic pentylenetetrazole: an in vitro study.

1. Rats were chemically kindled by systemic administration of pentylenetetrazole (PTZ) every 48 h. An initially subthreshold dose that did not elicit a motor response when first applied caused severe epileptiform seizures when the animal was kindled. Once kindled, animals continued to respond to the initially subthreshold dose with a full-blown seizure for > 2 mo, even when regular administration ceased for > or = 1 mo. 2. In neocortical slices taken from kindled rats, low-intensity electrical stimulation evoked generation of prolonged (hundreds of milliseconds) paroxysmal extracellular field potentials and intracellular depolarizing potentials, indicating synchronized activity of large populations of neurons. This hyperexcitability usually appeared as an all-or-none event of variable latency. In a few cases it increased gradually with increasing stimulus intensity. The intensity of the paroxysmal response was greatly enhanced by application of gamma-aminobutyric acid-A (GABAa) receptor blockers to the bath. 3. Intracellular recordings revealed that PTZ-kindled cells differ from normal cells in their higher input resistance (42.4 + 13.6 vs. 26.4 + 9.2 M omega, mean +/- SE). Spikes generated by kindled cells differed significantly from those in normal cells in that they were of longer duration (1.65 + 0.3 vs. 1.40 + 0.15 ms) and had a slower maximal rate of fall (103 + 29.7 vs. 126 + 20.8 volts/s). 4. Injection of the lidocaine derivative QX-314 to the recorded neurons (100 mM) blocked the fast Na+ spikes. Under these conditions slow spikes, probably Ca2+ mediated, were evoked from the soma in neurons from kindled but not from normal cortex. 5. The role of N-methyl-D-aspartate (NMDA) receptors in generating paroxysmal events was evaluated by application of 20 microM 2-amino-5-phosphonovaleric acid, a specific blocker of this glutamate receptor type. Blockage of NMDA receptors cut short the paroxysmal field potentials but did not prevent their generation. Intracellularly recorded paroxysmal responses were also cut short but not abolished by intracellular hyperpolarization. 6. In slices from kindled animals intracellular responses in neurons of deeper layers differed markedly from those of superficial cells. In deep neurons, responses resembled those generated by neocortical neurons exposed to GABAergic blockers. A low-intensity stimulus to the white matter evoked an excitatory postsynaptic potential (EPSP) followed with variable latency by a paroxysmal depolarizing shift that reversed at suprathreshold membrane potentials and on which superimposed repetitive firing was always evident.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Evaluation of a hyperbaric system to be used in conjunction with a fluorometer.

A high-pressure chamber that can be used inside the sample chamber of a spectrofluorometer is described and some performance characteristics are presented. The chamber body, constructed of 316 stainless steel, is temperature regulated using resistive heating elements and a microprocessor-based proportional integral derivative controller. The chamber holds a standard 1-cm2 cuvette that indexes with an electromagnetic stirrer. Injection of different solutions into the closed and pressurized (6.8 MPa) vessel is accomplished by computer-controlled, low-volume solenoids attached to separate microliter injection ports. Repetitive injections of fluids down to a volume of 7 microliters are possible in the pressurized chamber. Temperature stability of the chamber is +/- 0.2 degrees C at atmospheric or elevated pressure. However, during the initial phase (first 3 min) of pressurization, at a compression rate of 0.62 MPa/min, a 0.23 degrees C/min increase in temperature occurs. The chamber windows depress the relative intensity of the emitted light by approximately 20% for visible light and 40% for near UV; however, total sensitivity of the system is sufficient to accomplish most determinations while maintaining a good signal-to-noise ratio. This system can be used to evaluate the response of several molecular and cellular events during compression and at depth with the use of various fluorometric probes.

Atmosphere Exposure Chambers↗
PubMed1992

Effects of anticonvulsant drugs on axonal conduction in mammalian corpus callosum.

The frequency-dependent effect of various anticonvulsant drugs on the conduction in central axons was studied in the corpus callosum of rat and guinea pig brain slices from the parietal region. Extracellularly recorded compound action potentials (CAPs) were evoked by either single stimulus or high frequency stimulation (40-80 Hz). The CAP in rats consisted of an early component (fast axons, 1.2-1.8 m/s) and a late component (slow axons, 0.5-0.7 m/s), while in the guinea pig only the slow phase was observed. Diphenylhydantoin increased the latency of a single response by 10%, and had no effect on the CAP amplitude. In contrast, both phenobarbital and pentobarbital reduced the amplitude of singly evoked CAPs. Stimulation at high frequency alone decreased the CAP amplitude by 10-20%. Identical stimulation in the presence of the drugs further suppressed the CAP amplitude by an additional 31%, with varying degree of drug efficacy. The depressant effect was significant for the slow axons but the fast axons were virtually unaffected by any of the drugs. The results are consistent with the hypothesis that the antiepileptic drugs DPH, Phe and Pnt may block axonal conduction from an epileptic focus into neighbouring areas of the brain.

Action Potentials↗
PubMed1992

Synaptic transmission at high pressure: effects of [Ca2+]o.

1. The effects of pressure on synaptic currents were examined in crayfish abdominal muscles. 2. Helium pressure (10.1 MPa) considerably decreased extracellularly-recorded excitatory junctional potentials associated with increased short-term facilitation. 3. These effects could be mimicked by a reduction of [Ca2+]o, and partially compensated by an increase in [Ca2+]o. 4. Pressure also reduced the amplitude of the extracellular nerve terminal potentials (ENTP) by up to 25%, and significantly increased synaptic delay in a [Ca2+]o-dependent manner. 5. The interaction between compression and various [Ca2+]o were analysed in terms of an existing model of transmitter release. The results were consistent with the hypothesis that high pressure decreases the maximal Ca2+ influx into nerve terminals. 6. The decreased ENTP and increased synaptic delay suggest that additional processes may be involved in pressure effects on synaptic transmission.

Animals↗
PubMed1992

High pressure effects on reflexes in isolated spinal cords of newborn rats.

High pressure induces hyperexcitability and convulsions in both intact and decerebrated animals. However, pressure suppresses synaptic transmission in isolated invertebrate preparations. We examined the effect of high pressure on monosynaptic (MSR) and polysynaptic (PSR) reflexes in isolated spinal cords of newborn rats. Reflex activity was recorded extracellularly from the cut ends of the lumbar ventral roots L3-L5 following stimulation of the corresponding dorsal roots. Increasing the stimulus frequency from 0.1 to 2.0 Hz reduced the amplitude of both reflexes by 75%. High pressure (10.1 MPa helium) did not affect this phenomenon. Pressure had no effect on MSR amplitude, but increased PSR amplitude by 30%. For MSR, pressure increased the latency by 25%, duration by 20%, and rise time by 25%. Pressure abolished the moderate (119 +/- 4.5%, mean +/- SEM) posttetanic potentiation observed at 0.1 MPa. For the curve relating MSR amplitude to [Ca2+]o, high pressure produced a slight rightward shift of 0.25 mM without affecting its saturation level. These data suggest that the response of vertebrate central synapses to pressure may be different from previously described invertebrate synapses. Alternatively, if synaptic potentials are reduced at high pressure, other processes that determine excitability must be invoked to account for the relatively stabile reflex response.

Animals↗
PubMed1992

A system for saturating in vitro preparations with high pressure O2, He, H2, and mixtures.

Saturation of a liquid with gas before perfusing a tissue or cellular preparation under pressure can be achieved by bubbling the gas through the liquid. A container for this purpose that is housed in the pressure chamber with the preparation allows saturation of the liquid under hyperbaric conditions. Sealing the container allows saturation with a gas different from the gas used to compress the pressure chamber. If the pressure within the sealed container is maintained at a slightly higher level, the bubbling gas can also provide the driving force for the liquid to flow to the preparation. Based on this concept, an apparatus was built and tested to pressures of 6.8 MPa. This paper describes the saturator and the associated circuitry used to control bubbling gas pressure relative to the pressure vessel, gas flow through the saturator, and liquid flow to the preparation. A special application in the case of hydrogen gas is described, where this system has added safety advantages.

Equipment Design↗
PubMed1991

High CO2-bicarbonate buffer modifies GABAergic inhibitory effect at the crayfish neuromuscular synapse.

gamma-Aminobutyric acid (GABA) activated channels have a considerable permeability to bicarbonate ions (HCO3-), which might alter the efficacy of chloride-dependent synaptic inhibition. Saturation of the bicarbonate-buffered physiologic solution with 15% CO2/85% O2 increased the depolarizing inhibitory postsynaptic potential (IPSP) amplitude in crayfish muscle by 290% due to a shift of +8.33 mV in its reversal potential. Consequently, the normal inhibition exerted by the IPSP on the excitatory postsynaptic potential is reversed to large excitation.

Animals↗
PubMed1991

Interaction of Ca-channel blockers and high pressure at the crustacean neuromuscular junction.

Exposure to high pressure causes a significant depression of synaptic transmission. We examined the effects of various Ca-channel blockers and their interaction with high pressure on excitatory neuromuscular junction currents (EJCs) of lobster abdominal muscles. Reduced [Ca2+]o to half of normal concentration or exposure to 40-60 microM CdCl2, 10-20 microM NiCl2 and 1 microM omega-conotoxin decreased EJCs by 50%. Nifedipine, Nitrendipine and Bay K-8644 were ineffective. Either Ca-blockers or reduced [Ca2+]o, enhanced EJC suppression exerted by high pressure. The data suggest that high pressure primarily affects Ca2+ inflow at the presynaptic terminals through N-type voltage-gated Ca-channel.

Animals↗
PubMed1991

A 23187-stimulated calcium uptake and GABA release by cerebrocortical synaptosomes: effects of high pressure.

Guinea pig cerebrocortical synaptosome preparations were used to study the effect of compression to 62 ATA on 45Ca2+ uptake and [3H]GABA release using a calcium ionophore A 23187, which bypasses the voltage-sensitive calcium channel. Pressure was found to exert a suppressive effect on the A 23187-induced release of [3H]GABA, while having no significant effect on A 23187-stimulated 45Ca2+ uptake. On the other hand, both depolarization-induced 45Ca2+ uptake and [3H]GABA release were inhibited by pressure exposure. These results suggest that pressure may suppress GABA release by affecting pre-synaptic events subsequent to calcium influx.

Animals↗
PubMed1991

High pressure reduces pH sensitivity of respiratory center in isolated rat brainstem.

We examined the effect of high pressure (10.1 MPa) on the sensitivity of the respiratory center to alterations in pH (range 5.8-7.6) which were obtained by varying either PCO2 or [HCO3-] in superfused Krebs solution. Isolated rat brainstem-spinal cord preparations were placed in a pressure chamber and respiratory-related motor neuron activity was recorded from severed ventral roots C1 and C5. At atmospheric pressure, respiratory burst frequency in both C1 and C5 varied inversely with pH. Only the time integral of a single C5 response was sensitive to acidification. High helium pressure reduced by 60% the sensitivity of the respiratory frequency to alteration in pH, while the time integral of both C1 and C5 responses became independent of PCO2, causing the relative respiratory drive between the two roots to change. These modifications in the chemoresponse of the respiratory center may contribute to the respiratory difficulties encountered under high pressure conditions.

Animals↗
PubMed1991

Barbiturate alteration of respiratory rhythm and drive in isolated brainstem-spinal cord of newborn rat: studies at normal and hyperbaric pressure.

High pressure and anaesthetic agents are mutual antagonists in intact animals, but antagonism is not observed in isolated nerve cells. In order to test the hypothesis that a neural network might display pressure-anaesthetic antagonism not found in simpler systems, we have examined the effects of pentobarbitone at normal pressure and at 10.1 MPa helium pressure on the rhythmic activity of medullary respiratory centres of isolated brainstem and spinal cord from 0-3 day old rats. Pentobarbitone 5-80 mumol litre-1 depressed the frequency, amplitude and area of spontaneous bursts recorded from C5, reduced respiratory drive, and altered the response to trigeminal nerve root stimulation. Compression to 10.1 MPa decreased ventilatory frequency and respiratory drive, and either did not interact with or enhanced the depressant effects of pentobarbitone. Pentobarbitone and helium pressure altered the response to trigeminal nerve root stimulation in the same manner. The results are consistent with additive rather than antagonistic effects of pressure and a barbiturate on the determinants of output from the respiratory centre-motor neurone pathway. Pressure-anaesthetic antagonism may be a property unique to the neural circuitry which underlies awake behaviour and pressure-induced seizures, rather than reflecting a fundamental molecular-level antagonism.

Action Potentials↗
PubMed1991

High pressure modifies respiratory activity in isolated rat brain stem-spinal cord.

Exposure to hyperbaric pressure causes a constellation of motor disturbances and ventilatory difficulties in animals and humans. The present experiments were designed to examine the effects of hyperbaric pressure on the rhythmic activity of the respiratory center in the absence of peripheral sensory afferents by using the isolated brain stem-spinal cord preparation from newborn rats. In addition, we examined the effect of pressure on the response of the respiratory center to sensory input from the trigeminal and vagus cranial nerves. Hyperbaric pressure significantly depressed the mean inspiratory drive (frequency X time integral of single electrical bursts) in C5 but not in C1 ventral roots. Pressure also reduced the amount of inhibition on the respiratory activity normally exerted by trigeminal and vagal nerve stimulation and in some cases reversed it to excitation. It is concluded that in the absence of sensory input, exposure to hyperbaric pressure depresses central respiratory activity. However, in an intact system, it may alter the balance between excitation and inhibition and render the system hyperexcitable to the same sensory input.

Animals↗
PubMed1991

The effect of xanthine/xanthine oxidase generated reactive oxygen species on synaptic transmission.

The effect of reactive oxygen species generated by the interaction of xanthine and xanthine oxidase on synaptic transmission was examined at the squid giant synapse and the lobster neuromuscular junction. Exposure of these synaptic regions to xanthine/xanthine oxidase produced a significant depression in evoked release, with no change in either resting membrane properties or in the action potential. Addition of catalase to the xanthine/xanthine oxidase-containing media partially blocked the synaptic depression, indicating that H2O2 contributes to the synaptic changes induced by exposure to xanthine/xanthine oxidase. H2O2 applied directly to the perfusing media also produced a decrease in synaptic efficacy. The results demonstrate that reactive oxygen species, in general, depress evoked synaptic transmission.

Action Potentials↗
PubMed1990

Pentylenetetrazole-induced kindling is prevented by prior treatment with cysteamine.

We have previously demonstrated that in pentylenetetrazole (PTZ)-kindled rats, cysteamine causes prolonged depression of the kindled state. We now report that administration of cysteamine before or during the kindling process prevents attainment of the kindled state. This effect lasts long after cysteamine administration has ceased, suggesting that depletion or somatostatin may not be the only mechanism underlying cysteamine's effect on kindling. The results also support the likelihood that PTZ kindling primarily effects neocortical rather than limbic structures.

Animals↗
PubMed1990

Evidence for reduced presynaptic Ca2+ entry in a lobster neuromuscular junction at high pressure.

1. Previous studies have shown that hyperbaric pressure depresses synaptic transmission and have suggested that the effect is primarily on transmitter release. The present study analysed the effects of pressure at a crustacean neuromuscular junction. Changes in pressure were compared to changes in extracellular calcium concentration [Ca2+]o with respect to effects on excitatory junction potential (EJP) amplitude, time course, facilitation and potentiation. 2. The effects of 10.1 MPa pressure on EJP amplitude, facilitation and potentiation, but not time course, were mimicked by reducing [Ca2+]o to approximately one-half the normal level. 3. The effects of pressure and the interaction between compression and calcium concentration were analysed in terms of a model of transmitter release. The model assumes that release is dependent on internal calcium concentration, as modulated by both influx and removal processes; that calcium influx is a saturating function of [Ca2+]o; and that release and removal are saturating functions of [Ca2+]i. 4. The results were consistent with the hypothesis that increased pressure acts primarily to reduce calcium influx into the nerve terminal.

Animals↗