Kinetic theory of plasma sheaths surrounding electron-emitting surfaces.

A one-dimensional kinetic theory of sheaths surrounding planar, electron-emitting surfaces is presented which accounts for plasma electrons lost to the surface and the temperature of the emitted electrons. It is shown that ratio of plasma electron temperature to emitted electron temperature significantly affects the sheath potential when the plasma electron temperature is within an order of magnitude of the emitted electron temperature. The sheath potential goes to zero as the plasma electron temperature equals the emitted electron temperature, which can occur in the afterglow of an rf plasma and some low-temperature plasma sources. These results were validated by particle in cell simulations. The theory was tested by making measurements of the sheath surrounding a thermionically emitting cathode in the afterglow of an rf plasma. The measured sheath potential shrunk to zero as the plasma electron temperature cooled to the emitted electron temperature, as predicted by the theory.

Preparation of asymmetric, cerebroside sulfate-containing phospholipid vesicles.

A procedure is described which inserts asymmetrically cerebroside sulfate ('sulfatide') into the outer leaflet of bilayered phospholipid vesicles. Cerebroside sulfate is adsorbed onto a cellulose, filter-paper support and, when incubated with phosphatidylcholine vesicles is transferred to and inserted into the outer leaflet of these vesicles. This transfer occurs at, or above the transition temperature of the phospholipid and follows a similar pattern with small or larger ('fused') unilamellar vesicles. The transfer is linear with time for 1-2 h and is maximal after about 6 h, when the sulfatide content reaches about 6 mol% of the total quantity of phospholipid, corresponding to about 10 mol% of the phospholipids present in the outer layer. Initial rates of sulfatide transfer were somewhat increased when the vesicles contained a positively charged lipid (e.g. stearylamine) and decreased when this lipid was negatively charged (e.g. dicetyl phosphate) or hydrophobic (e.g. cholesterol). Divalent ions markedly inhibited sulfatide transfer and monovalent ions did so to a lesser degree. Once incorporated into the outer leaflet of the vesicle, the sulfatide could not be removed by washing with buffer, 1 M NaCl or 1 M urea.

Cycloleucine blocks NMDA responses in cultured hippocampal neurones under voltage clamp: antagonism at the strychnine-insensitive glycine receptor.

1. Radioligand binding studies have demonstrated that the neutral amino acid cycloleucine may act as a competitive antagonist at the glycine modulatory site on the N-methyl-D-aspartate (NMDA) receptor complex. In the present study, we examined the effects of cycloleucine on NMDA-evoked inward current responses in dissociated hippocampal neuronal cultures using the whole cell voltage-clamp technique. 2. In the presence of 1 microM glycine, cycloleucine caused a reversible, dose-dependent inhibition of NMDA responses with an IC50 of 24 microM. An increase in glycine to 100 microM resulted in a shift to the right of the cycloleucine concentration-effect curve (IC50, 1.4 mM). However, with cycloleucine concentrations less than or equal to 100 microM, a fraction of the block could not be overcome by glycine even at concentrations as high as 1 mM. 3. The cycloleucine block was unaffected by shifts in the holding potential (-60 to +60 mV), and there was no effect of cycloleucine on the reversal potential of the NMDA-evoked current. 4. Cycloleucine failed to effect kainic acid- and quisqualic acid-evoked currents at concentrations which inhibited NMDA responses. 5. We conclude that cycloleucine is a potent and selective antagonist of NMDA-receptor mediated responses. Although this effect occurs in part via competitive antagonism at the glycine modulatory site, the cycloleucine block cannot be completely reversed by glycine indicating an interaction with an additional site on the receptor-channel complex.

Neuronal effects of water-soluble contrast agents.

The in vitro rat hippocampus slice preparation has been utilized to examine the direct neurotoxicity of water-soluble contrast agents. Intraneuronal recordings were obtained from pyramidal cells in the CA1 field of rat hippocampus slices. Synaptic activity was evoked by Schaffer's collateral stimulation. The effects of Na-diatrizoate and metrizamide were studied. Test solutions were 300 to 345 mOsm and had iodine concentrations of 22.5 to 30 mg I/ml which are probably near clinical concentrations. The two effects of the contrast agents are apparent within 10 minutes and reversible within 30 to 45 minutes. The first is an epileptogenic property reflected by repetitive action potentials arising from an early prolonged depolarization. The second effect is a depression of electrical activity characterized by hyperpolarization of the resting membrane potential. Na-diatrizoate predominantly produced the first effect. Metrizamide principally produced the second effect. These results indicate that contrast agent seizure activity is not due to hyperosmolarity but a more direct chemical effect. The depression, however, may be related to a hyperosmolar effect. The differences between the dominant effects of the ionic vs. nonionic agents observed in these experiments seem to correlate with clinical experience and may indicate the etiology of central nervous system neurotoxicity of these drugs.

Neurotoxic effects of water-soluble contrast agents on rat hippocampus.

Electrical activity in cells directly exposed to water-soluble radiographic contrast agents was investigated by intracellular and extracellular recordings from neurons in in vitro rat hippocampus slices. Measurements included extracellular field potentials, intracellular resting membrane potential and membrane conductance, postsynaptic events, action potential configurations and spontaneous electrical activity. The neurons were exposed to test solutions of an ionic contrast agent, sodium diatrizoate, and a nonionic contrast agent, metrizamide, as well as control solutions. The ionic contrast agent produces bursts of action potentials having epileptogenic characteristics which is temporally followed by a depression of all electrical activity. The nonionic contrast agent produces minimal convulsive-like electrical bursts, but does produce a consistent depression of transmembrane electrical potentials, though in a lesser degree than the ionic contrast agents. The excitatory electrical events appear to be related to large depolarizing post-synaptic events while the later electrical depression is at least partially due to hyperpolarization. The depressing effects may be related to the hyperosmolality of the test solutions; however, no excitatory changes are related to hyperosmolality. These results provide the initial data on the neurotoxicity of water-soluble contrast agents at the intraneuronal level.

Neurotoxic effects of water-soluble contrast agents on rat hippocampus: extracellular recordings.

Synaptically evoked extracellular field potentials were obtained from the pyramidal cell layer of the Cal field of rat hippocampus slices. Synaptic activity was evoked by Schaffer's collateral stimulation. The effects of the water-soluble contrast agents Na-diatrizoate and metrizamide, as well as control solutions of NaCl and sucrose, were studied. Test solutions were 300-345 mOsm and had iodine concentrations of 3-30 mg I/ml. The effects of test solutions are apparent within 10 minutes and reversible within 30-45 minutes. Control recordings have a small positive potential, followed by a large negative spike and a final slow positive wave. Contrast agents have two effects. The first is an epileptogenic property characterized by repetitive negative spikes arising from an extended slow positive field. The second effect is a depression characterized by a reduction in the amplitude of the synaptically evoked fields, particularly the negative spikes. Na-diatrizoate predominately produces the first effect, while metrizamide principally produces the second. Hyperosmolar solutions only produce depression. These results correlate well with the clinical setting where Na-diatrizoate is a potent convulsant, while metrizamide produces symptoms compatible with neuronal depression. These results indicate that contrast agent seizure activity is not due to hyperosmolarity but to a more direct chemical effect. The depression, however, may be related to a hyperosmolar effect.

Effects of phenytoin on pyramidal neurons of the rat hippocampus.

The effects of phenytoin (35 micrograms/ml) on membrane properties and inhibitory postsynaptic potential (IPSPs) in CA1 and CA3 pyramidal neurons of the in vitro rat hippocampus were examined. No significant change was observed on input resistance or resting membrane potential. Action potential amplitude, overshoot, rate of rise and rate of decay were decreased. IPSP conductance increase and reversal potential, evoked in CA3 cells through mossy fiber stimulation and in CA1 cells through recurrent and Schaffer's collateral stimulation, were unaffected.

Some factors that influence the decrement in the response to GABA during its continuous iontophoretic application to hippocampal neurons.

The response decrement that occurs during continuous iontophoretic application of GABA to hippocampal neurons was characterized by intracellular methods in the rat hippocampal slice. Using several paradigms that compared the responses to GABA with those to poorly transported analogues, we then identified a large component of this decrement that appeared to be independent of GABA uptake and metabolism, and that is probably independent of intracellular chloride accumulation as well. This decrement, which both developed and recovered with half times that average between 3 and 5s, is too brief to directly account for long-term plasticity of the GABA synapse. However, its time course is appropriate to participation in the development of cellular responses to brief flurries of GABA-mediated inhibitory postsynaptic potentials that may occur normally, or that may occur abnormally during a seizure or artificial tetany.

Arachidonic acid participates in the anoxia-induced increase in mEPSC frequency in CA1 neurons of the rat hippocampus.

Patch clamp in the whole cell configuration was used to examine the effects of a variety of agents that influence arachidonic acid metabolism on vesicular glutamate release in CA1 neurons of rat hippocampal slices. As previously demonstrated, anoxia induced a significant increase in the frequency of spontaneous glutamate-mediated miniature excitatory postsynaptic currents (mEPSCs) during the first 5 min following anoxia. This increase in frequency was almost completely abolished if slices were preincubated in artificial cerebral spinal fluid (ACSF) containing the phospholipase C/A2 inhibitor, bromophenacyl-bromide (BPB; 20 microM) or the cyclooxygenase inhibitors, indomethacin (20 microM) and piroxicam (10 microM). This observation may be important to our understanding of the neuroprotective action of these agents. These data suggest that arachidonic acid (AA) and its cyclooxygenase products or by-products (oxygen free radicals) contribute to vesicular glutamate release during the early phase of anoxia.

Adenosine antagonists prevent hypoxia-induced depression of excitatory but not inhibitory synaptic currents.

Hypoxia induces depression of excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs) in CA1 neurons of the hippocampus. The effect of antagonists that act at the A1 adenosine receptor on hypoxia-induced depression of EPSCs and IPSCs were examined in hippocampal slices with the patch clamp technique (whole-cell configuration). The A1 receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (200 nM) and 8-phenyltheophilline (8-PT) (10 microM) significantly prevented depression of EPSCs by hypoxia but failed to protect IPSCs. This result suggests that the hypoxia-induced depression of the EPSC involves the activation of adenosine receptors (possibly of the A1 subtype), whereas depression of the IPSC results from a different mechanism.

Nitric oxide modulates synaptic glutamate release during anoxia.

The ability of nitric oxide to enhance vesicular glutamate release during anoxia was examined in the present study. Whole-cell patch clamp recordings were obtained from CA1 pyramidal neurons in rat hippocampal slices perfused in media containing tetrodotoxin. These cells exhibit spontaneous inward currents previously identified as glutamatergic miniature excitatory postsynaptic currents (mEPSCs). The frequency of these mEPSCs increases during exposure to anoxia. The anoxia-induced increase in frequency is reduced when experiments are performed in the presence of the competitive nitric oxide (NO)-synthase inhibitors N(G)-nitro-L-arginine methyl ester and N(G)-nitro-L-arginine, as well as reduced hemoglobin. Arginine reversed the suppression by the NO-synthase inhibitors. The N-methyl-D-aspartate (NMDA) receptor antagonists 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid and MK-801 also suppressed the anoxia-induced increase in mEPSC frequency. These data indicate that NMDA receptor-activated NO production may enhance vesicular synaptic glutamate release, which would in turn contribute to excitotoxicity during hypometabolic states.

Evidence for orbital deformation that may contribute to monocular blindness following minor frontal head trauma.

Traction injury to the optic nerve and vasa nervorum is the suggested etiology for monocular blindness following trivial frontal trauma. Holographic interferometry was used on human skulls to demonstrate orbital deformation in response to nondestructive frontal loading. The findings suggest an additional mechanism for energy dissipation and therefore for optic nerve injury following frontal impact.

Inflection-point method of interpreting emissive probe characteristics.

The use of emissive Langmuir probes in unmagnetized and weakly magnetized multidipole plasmas is investigated. It is shown that plasma potential, plasma electron temperature, and probe temperature can be determined from one probe characteristic curve. Data indicate that the inflection point of the current-voltage curve gives the plasma potential to an accuracy the order of the probe temperature Tw/e for weak probe emission. Effects of space-charge limiting and contamination of the probe are presented.