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Biomedical subjects

M Segal

Publications and source records attributed to M Segal.

At least 253 records · Page 14Linked to original sources
PubMed1984

Rat hippocampal neurons in culture: voltage-clamp analysis of inhibitory synaptic connections.

Inhibitory postsynaptic potentials (IPSPs) recorded at room temperature in cultured rat hippocampal neurons had the same reversal potential as Cl--dependent voltage responses to gamma-aminobutyric acid (GABA). The IPSPs had a relatively short latency and long duration and could be evoked for hours without change in their properties. They were consistently depressed by picrotoxin applied near cell bodies of the neurons under study. Postsynaptic cells exhibiting IPSPs were voltage clamped with two electrodes for the purpose of studying the properties of evoked inhibitory postsynaptic currents (IPSCs). The IPSCs shared the same reversal potential and sensitivity to [Cl-]i as was observed with membrane current responses to GABA. They were both depressed by picrotoxin, with little if any change in the kinetics of ion channel activity either estimated from fluctuation analysis of drug-depressed current responses to GABA or calculated from semilogarithmic plots of IPSC decay. The decay of the IPSC was well fitted by a single exponential with a time constant of about 20 ms, which corresponded closely to the estimated average duration of an ion channel activated by GABA. IPSC decay was sensitive to the potential at which the cell was held, increasing by up to 50% in some cells clamped at positive potentials relative to values obtained at the level of the resting potential. IPSCs were enhanced in amplitude by diazepam, which also prolonged their time constant of decay. Diazepam potentiated membrane current responses to GABA and fluctuation analysis of potentiated responses indicated that the drug effects could be accounted for by an increase both in estimated channel duration and channel frequency. IPSCs were also altered by pentobarbital, which markedly prolonged their time constant of decay with little if any change in their amplitude. Pentobarbital enhanced current responses to GABA, an effect that could be accounted for primarily in terms of a pronounced increase in estimated channel lifetime. None of the drugs used in the present study affected the elementary conductance estimated from fluctuation analysis of GABA-evoked current response. The results suggest that IPSPs and IPSCs evoked in these cultured hippocampal cells are mediated by GABA, about 1,700 Cl- ion channels are activated at the peak of the synaptic conductance, and clinically important drugs act postsynaptically on the kinetics of the channels so as to change the amplitude and/or time course of the synaptic conductance.

Animals↗
PubMed1984

A transient potassium conductance regulates the excitability of cultured hippocampal and spinal neurons.

Cultured mouse spinal cord and rat hippocampal neurons were voltage clamped with a two-electrode system in the presence of tetrodotoxin (1 to 3 microM) and tetraethylammonium (25 mM). Depolarizing voltage commands from holding potentials negative to -50 mV evoked a transient outward current response that peaked within 10 msec and decayed exponentially with a time constant of 10 to 40 msec. The current was inactivated by holding at potentials more positive than -50 mV but could be reactivated by brief hyperpolarizing prepulses (20-msec steps to -90 mV reactivated 50%). The inversion potential of the tail current evoked in a double-step protocol was -70 to -75 mV, and this shifted in a depolarizing direction with elevated [K+]0. The transient outward current was blocked by external application of 4-aminopyridine (4-AP) with an IC50 of 2 mM. In experiments under current clamp, 4-AP suppressed an initial transient rectification of the electrotonic potential recorded in response to depolarizing current and reduced the threshold for single and repetitive action potentials. Thus, a transient K+ conductance similar to IA of molluscan neurons may serve to regulate the excitability of some central mammalian neurons. Depression of this conductance by 4-AP could contribute to the drug's convulsant effects in vivo.

Action Potentials↗
PubMed1983

Physiological properties of ascending locus coeruleus axons in the squirrel monkey.

Discharge activity was recorded extracellularly from individual neurons of the nucleus locus coeruleus in anesthetized squirrel monkeys. These cells exhibited long-duration (2-3 ms) action potentials and discharged spontaneously in a slow (0.2-2 Hz) irregular fashion. Stimulation of the lateral hypothalamus evoked antidromic responses at latencies of 10-20 ms, indicating conduction velocities of over 1 m/s in some cases. The mean refractory period for these axons was 2.6 ms. When the rate of hypothalamic stimulation was increased from 1 to 10 Hz there was a 15-20% increase in antidromic latencies. These properties are similar to those previously observed for rat LC neurons, except that conduction velocities are higher in monkey.

Animals↗
PubMed1983

Application of high-performance liquid chromatography with electrochemical detection to the determination of catecholamines in microdissected regions of the rat brain.

High-pressure liquid chromatography (HPLC) with electrochemical detection was applied for measurement of catecholamines in microdissected tissues from discrete brain regions. Brain areas were dissected, extracted and processed for HPLC assay without further purification. The advantage of this method is its simplicity and relatively low cost and may therefore be applied to the measurement of amines in brain micropunches.

Animals↗
PubMed1983

Cholesterol granuloma in a thyroglossal duct cyst. A case report.

A case of cholesterol granuloma (CG) in a thyroglossal duct cyst is presented. The main pathogenic theories of this entity are described. It is suggested that chronic or recurrent infection and inflammation may play the major part in the pathogenesis of CG.

Adult↗
PubMed1983

Amphotericin B selection of mutant Chinese hamster cells with defects in the receptor-mediated endocytosis of low density lipoprotein and cholesterol biosynthesis.

This paper describes a rapid and efficient two-step procedure for the isolation of mutant cells with defects in receptor-mediated endocytosis. The procedure takes advantage of two fungal metabolites, compactin (ML236B), a potent inhibitor of cholesterol biosynthesis, and amphotericin B, a polyene antibiotic that forms toxic complexes with sterols in membranes. Mutagen-treated Chinese hamster ovary cells were preincubated overnight in a medium containing mevalonate, low density lipoprotein (LDL), and compactin (Mev/LDL/Com). At the end of the preincubation period, wild-type cells were cholesterol replete while mutant cells that could not utilize the cholesterol in LDL were cholesterol deficient. Subsequent incubation with amphotericin B for 6 hr killed most of the wild-type cells. After a second round of Mev/LDL/Com-amphotericin B selection, endocytosis-defective clones appeared at a frequency of approximately equal to 2.6 X 10(-5). Some of these clones expressed LDL receptor-defective phenotypes and fell into one of two previously defined classes of mutation. Sensitivity of the mutants to infection by vesicular stomatitis virus suggested that the mutations do not disrupt the coated pit-coated vesicle pathway of endocytosis. Minor modifications in the Mev/LDL/Com-amphotericin B selection permit the isolation of cholesterol auxotrophs and might allow the isolation of conditional-lethal mutations. Because LDL can be coupled to ligands that bind to receptors other than the LDL receptor, Mev/LDL/Com-amphotericin B selection may permit the isolation of mutant cells with defects that specifically disrupt other endocytic pathways.

Amphotericin B↗
PubMed1983

Rat hippocampal neurons in culture: responses to electrical and chemical stimuli.

Intracellular activity was recorded from dissociated rat hippocampal neurons maintained in tissue culture conditions for 4-6 wk. The cells developed dense interconnections and had typical morphological characteristics similar to hippocampal neurons in situ. The recorded neurons possessed similar electrophysiological properties to those observed in situ or in a slice preparation. Their input resistance (42 M omega), resting membrane potential (-60 mV), membrane time constant (16.2 ms), total electrotonic length (0.92), and spike size (68.3 mV) were similar to values obtained in hippocampal cells in a slice. The connections among adjacent neurons were largely inhibitory. The inhibitory postsynaptic potentials (IPSPs) had longer durations than excitatory postsynaptic potentials (EPSPs) when these were detected. Synaptic delay varied between 0.3 and 3.0 ms. There were no electrotonic connections among neurons. Reciprocal connections were common. Most neurons reacted to acetylcholine (ACh) by an increase in frequency of spontaneous EPSPs, action-potential discharges, and IPSPs. Concurrently, there was a marked reduction in the magnitude of the evoked PSPs tested in pairs of cells. This effect is probably presynaptic to the recorded neurons. A statistical analysis of quantal properties of the synaptic interactions among neurons revealed that ACh causes a reduction of magnitude of PSPs by reducing the number of releasing elements (m). This effect is different from the reduction of evoked PSPs caused by postsynaptic depolarization.

Acetylcholine↗
PubMed1983

Cross-national differences in dialysis rates.

The dialysis treatment rate is more than 50 percent higher in the United States than it is in any West European nation. Relman and Rennie's analysis of this difference in rates raised the possibility that the extra care provided in the United States is unnecessary and is partially attributable to the existence of a private market for renal dialysis services. Their analysis ignores the effect of race on treatment needs in the United States. About 50 percent of the difference observed in rates between the American experience and the European maximum can be attributed to differences in the black/white composition of the populations. Most of the remaining difference in rates appears to be due to European policies that prohibit or severely limit access to dialysis by the elderly and those potential patients with significant medical complications.

Adult↗
PubMed1982

Multiple action of acetylcholine at a muscarinic receptor studied in the rat hippocampal slice.

Responses of hippocampal pyramidal cells to topical application of acetylcholine (ACh) were measured in the in vitro hippocampal slice preparation. ACh but not cyclic GMP produced a short-latency hyperpolarization associated with a decrease in input resistance. This was followed by a long-latency but long duration depolarization associated in some cells with an increase in input resistance. This change in resistance followed the depolarization and outlasted it by 5--20 min, until complete recovery. During the depolarization there was a reduction in magnitude of EPSPs produced by activation of the Schaffer collateral excitatory afferents. The reversal potential for the hyperpolarization was about -95 mV, and it was blocked by 4-aminopyridine. The depolarization, but not the hyperpolarization was markedly attenuated in slices maintained in low (25 degrees C) temperature. The responses to ACh were blocked by atropine but not by D-tubocurarine. The hyperpolarization as well as the depolarization were present in slices treated with tetrodotoxin (TTX)., but were reduced in slices superfused with a low Ca2+-high Mg2+ medium, and in slices treated with Mn2+ and Co2+ ions. It is suggested that ACh causes a fast increase in gK+, followed by a long-lasting energy-dependent depolarization associated with action potential discharges, a decrease in conductance and a suppression of EPSPs.

4-Aminopyridine↗
PubMed1982

Intracellular analysis of a postsynaptic action of adenosine in the rat hippocampus.

The effects of topical or iontophoretic application of adenosine (AD) were studied by means of intracellular recording techniques in rat hippocampal slices. AD applied in a microdrop containing up to 0.1 nmol of AD produced a 7 +/- 0.7 mV hyperpolarization associated with a 30% decrease in input resistance of the recorded neurons. The hyperpolarization was dependent on the resting membrane potential and had an apparent reversal potential of about -90mV. These effect were still present when synaptic activity was blocked. AD also caused a marked reduction in the magnitude of synaptic potentials in the recorded neurons. Iontophoretic application of AD in dendritic regions caused a suppression of EPSP without affecting resting membrane potential ionotophoresis of AD onto somata produced both hyperpolarization and decreased EPSP. It is suggested that AD produces both presynaptic depression of transmitter release and postsynaptic increase in K+ conductance.

4-Aminopyridine↗
PubMed1982

Evaluation of the role of oxygen radicals in polymorphonuclear leukocyte aggregation.

oxygen radicals have been shown to alter granulocyte function by injury to the cell membrane or cytoskeleton. We have investigated the effect of such injury on the aggregation of granulocytes upon C5a or PMA stimulation. Granulocyte aggregation was not altered in the presence of the oxygen radical scavengers SOD, catalase, mannitol, or benzoate. To test whether oxygen radicals were required for aggregation, we evaluated three patients with chronic granulomatous disease of childhood. The response of PMNs from these patients was no different from controls. Hydrocortisone, an inhibitor of both granulocyte aggregation and oxygen radical generation, was then studied to decide whether its impairment of radical production contributed to its effect on aggregation. Five times the concentration of hydrocortisone needed to inhibit radical generation was required to impair aggregation by 50%. In addition, hydrocortisone was able to impair the aggregation of the PMNs of a patient with chronic granulomatous disease. These data suggest that oxidative injury to the cell membrane or cytoskeleton does not significantly contribute to the aggregation of granulocytes. In addition, inhibitors of aggregation, such as hydrocortisone, work through mechanisms other than by scavenging radicals.

Benzoates↗