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E A Newman

Publications and source records attributed to E A Newman.

At least 37 records · Page 2Linked to original sources
PubMed1989

Spatial buffering of light-evoked potassium increases by retinal Müller (glial) cells.

Activity-dependent variations in extracellular potassium concentration in the central nervous system may be regulated, in part, by potassium spatial buffering currents in glial cells. The role of spatial buffering in the retina was assessed by measuring light-evoked potassium changes in amphibian eyecups. The amplitude of potassium increases in the vitreous humor was reduced to approximately 10 percent by 50 micromolar barium, while potassium increases in the inner plexiform layer were largely unchanged. The decrease in the vitreal potassium response was accurately simulated with a numerical model of potassium current flow through Müller cells, the principal glial cells of the retina. Barium also substantially increased the input resistance of Müller cells and blocked the Müller cell-generated M-wave, indicating that barium blocks the potassium channels of Müller cells. Thus, after a light-evoked potassium increase within the retina, there is a substantial transfer of potassium from the retina to the vitreous humor by potassium current flow through Müller cells.

Ambystoma↗
PubMed1988

Model of potassium dynamics in the central nervous system.

A one-dimensional numerical model of potassium dynamics in the central nervous system is developed. The model incorporates the following physiological processes in computing spatial and temporal changes in extracellular K+ concentration, [K+]o: 1) the release of K+ from K+ sources into extracellular space, 2) diffusion of K+ through extracellular space, 3) active uptake of K+ into cells and blood vessels, 4) passive uptake of K+ into a cellular distribution space, and 5) the transfer of K+ by K+ spatial buffer current flow in glial cells. The following tissue parameters can be specified along the single spatial dimension of the model: 1) the volume fraction and tortuosity of extracellular and glial cell spaces, 2) the volume fraction of the cellular distribution space, 3) rate constants of active uptake and passive uptake processes, and 4) glial cell membrane conductance. The model computes variations in [K+]o and current flow through glial cells for three tissue geometries: 1) planar geometry (the retina and the surface of the brain), 2) cylindrical geometry (tissue surrounding a blood vessel), and 3) spherical geometry (tissue surrounding a point source of K+). For simple sources of K+, the performance of the model matches that predicted from analytical equations. Simulations of previous ion dynamics experiments indicate that the model can accurately predict ion diffusion and K+ current flow in the brain. Simulations of electroretinogram generation and K+ siphoning onto blood vessels suggest that unanticipated K+ dynamics mechanisms may be operating in the central nervous system.

Animals↗
PubMed1988

Potassium conductance in Müller cells of fish.

The distribution of potassium conductance across the surface of retinal glial (Müller) cells was determined in three species of fishes: two teleosts, the goldfish (Carassius auratus) and the alewife (Alosa pseudoharengus), and an elasmobranch, the spiny dogfish (Squalus acanthias). Potassium conductance was measured by monitoring cell depolarizations evoked by focal ejections of a 15 mEq/L K+ solution onto the surface of freshly dissociated cells. The K+ conductance distributions observed in these three species resembled those found previously in other animals with avascular retinas. In both alewife and dogfish, K+ conductance was highest in the endfoot; K+ conductance in the distal half of these cells ranged from 7.0 to 22.9% of the endfoot conductance. In goldfish, in contrast, K+ conductance was highest in the proximal region of the proximal process (114% of the endfoot conductance). As in the two other species, however, K+ conductance in goldfish was low in the distal half of the cell (7.6 to 40.1% of endfoot conductance). Mean input resistance values of isolated cells were as follows: goldfish, 12.5 M omega; alewife, 26.4 M omega; dogfish, 38.0 M omega. The high resistance of dogfish Müller cells lacking their endfeet (749 M omega) indicates that 95% of the cell membrane conductance is located in or near the endfoot in this species.

Animals↗
PubMed1988

Generation of the e-wave of the electroretinogram in the frog retina.

The e-wave and a delayed-OFF increase in extracellular K+ concentration are both maximum in the distal half of the inner plexiform layer. These responses also have similar latency, time-course, intensity-dependence, surround properties, and sensitivity to tetrodotoxin. Current source-density analysis of the e-wave reveals a current sink through the proximal retina, a source at the retinal surface, and, in some cases, a weaker source in the mid-retina. These results suggest a model for e-wave generation: delayed-OFF activity in proximal neurons releases K+, which enters Muller cells in the inner plexiform layer; a current exists Muller cells primarily via their endfeet, and the return flow through extracellular space produces the e-wave.

Action Potentials↗
PubMed1987

Does the release of potassium from astrocyte endfeet regulate cerebral blood flow?

Local increases in neuronal activity within the brain lead to dilation of blood vessels and to increased regional cerebral blood flow. Increases in extracellular potassium concentration are known to dilate cerebral arterioles. Recent studies have suggested that the potassium released by active neurons is transported through astrocytic glial cells and released from their endfeet onto blood vessels. The results of computer simulations of potassium dynamics in the brain indicate that the release of potassium from astrocyte endfeet raises perivascular potassium concentration much more rapidly and to higher levels than does diffusion of potassium through extracellular space, particularly when the site of a potassium increase is some distance from the vessel wall. On the basis of this finding, it is proposed that the release of potassium from astrocyte endfeet plays an important role in regulating regional cerebral blood flow in response to changes in neuronal activity.

Arteries↗
PubMed1987

Regulation of potassium levels by Müller cells in the vertebrate retina.

The membrane properties of Müller cells, the principal glial cells of the vertebrate retina, have been characterized in a series of physiological experiments on freshly dissociated cells. In species lacking a retinal circulation (tiger salamander, rabbit, guinea pig), the end-foot of the Müller cell has a much higher K+ conductance than do other cell regions. In species with retinal circulation (mouse, cat, owl monkey) the K+ conductance of the end-foot is greater than the conductance of the proximal process of the cell. In these species, however, the K+ conductance of the soma and distal process is equal to, or greater than, the end-foot conductance. Müller cells also possess four voltage-dependent ion channels, including an inward rectifying K+ channel. These membrane specializations may aid in the regulation of extracellular K+ levels by Müller cells in the retina. High end-foot conductance shunts excess K+ out through the end-foot, where it diffuses into the vitreous humor. In vascularized retinae, excess K+ may also be transferred to the ablumenal wall of capillaries, where it could be transported into the blood.

Animals↗
PubMed1987

Distribution of potassium conductance in mammalian Müller (glial) cells: a comparative study.

The distribution of K+ conductance across the surface of retinal Müller cells was determined in 5 mammalian species--rabbit, guinea pig, mouse, owl monkey, and cat--and in tiger salamander. Potassium conductance was measured by monitoring cell depolarizations evoked by focal ejections of a high-K+ solution onto the surface of freshly dissociated cells. This technique measured the total K+ conductance of a given cell region (regional conductance), i.e., the specific K+ conductance times the total surface area in that region. In mammalian species with avascular retinas (rabbit, guinea pig), the regional K+ conductance within the middle portion of the cell was only a fraction (10.6-28.9%) of the endfoot conductance, while the conductance of the distal (photo-receptor) end of the cell was approximately half (41.2-49.8%) the endfoot conductance. In 2 species with vascularized retinas (mouse and owl monkey), by contrast, the regional K+ conductance within the middle portion of the cell was as large as 125.5-129.8% of the endfoot conductance. In these cells the K+ conductance of the distal end was 68.3-82.9% of the endfoot value. In cat, a third vascularized species, the K+ conductance was highest (187.1% of the endfoot value) at the distal end of the cell. In tiger salamander, which has an avascular retina, the regional K+ conductance of all regions distal to the endfoot was only 2.4-15.7% of the endfoot value. Differences in the distributions of regional K+ conductance observed in the 6 species raise the possibility that in vascularized mammalian retinas, the high-K+ conductance of the middle portion of Müller cells is associated with retinal blood vessels. The results are consistent with the hypothesis that, in avascular species, Müller cells aid in regulating extracellular K+ levels by transferring (siphoning) excess K+ principally into the vitreous humor, while in at least some vascularized species (mouse, monkey), excess K+ is transferred by Müller cells into retinal capillaries, as well as into the vitreous.

Animals↗
PubMed1986

High potassium conductance in astrocyte endfeet.

The distribution of potassium conductance over the surface of freshly dissociated salamander astrocytes was determined by monitoring cell depolarizations evoked by focal increases in the extracellular potassium concentration. The specific potassium conductance of the endfoot processes of these cells was approximately tenfold higher than the conductance of other cell regions. This dramatically nonuniform conductance distribution may play an important role in the regulation of extracellular potassium levels by glia in the brain.

Animals↗
PubMed1986

Regional specialization of the membrane of retinal glial cells and its importance to K+ spatial buffering.

Electrophysiological experiments, obtained primarily from dissociated salamander cells, demonstrate that the K+ conductance of Müller cells is distributed in a highly nonuniform manner over the cell surface. A large fraction of the total cell conductance is localized to that portion of the endfoot process that faces the vitreous humor. Along the remainder of the cell, specific K+ conductance is larger in the outer plexiform layer than in neighboring regions. High-endfoot conductance directs K+ spatial buffering currents preferentially through the endfoot process, leading to an efficient form of spatial buffering termed K+ siphoning. Preliminary experiments suggest that the endfeet of astrocytes also have high K+ conductance.

Animals↗
PubMed1985

Light-evoked increases in extracellular K+ in the plexiform layers of amphibian retinas.

Recordings of light-evoked changes in extracellular K+ concentration (delta[K+]o) were obtained in the retinas of frog and mudpuppy. In eyecup preparations, various recording approaches were used and provided evidence for a K increase near the outer plexiform layer (distal K increase). This distal K increase could be pharmacologically dissociated from the well-known, large K increase in the proximal retina by the application of ethanol and gamma-aminobutyric acid. The distal K increase also often showed surround antagonism. A retinal slice preparation was used to permit electrode placement into the desired retinal layers under direct visual control and without the risk of electrode damage to adjacent layers. In the slice, a distinct distal K increase was found in the outer plexiform layer, in addition to the prominent K increase in the inner plexiform layer. Compared with eyecups, only weak K increases were found in the nuclear layers of the slice. This suggests that the K responses observed in the nuclear layers of eyecups may be generated by K+ diffusing along the electrode track from the plexiform layers. In the context of current models of ERG b-wave generation, the magnitude of the recorded distal K increase, compared with the proximal K increase, seems too small to give rise to the b-wave. However, the distal K increase may be differentially depressed by electrode dead space. It is also possible that if certain aspects of the models of b-wave generation were modified, then the observed distal K increase could give rise to the b-wave.

Animals↗
PubMed1985

Membrane physiology of retinal glial (Müller) cells.

Electrophysiological techniques were used to determine the ion selectivity properties and the spatial distribution of the membrane conductance of amphibian Müller cells. Membrane potential changes recorded during ion substitution experiments in frog (Rana pipiens) retinal slices demonstrated that the Müller cell K+:Na+ membrane permeability ratio is approximately 490:1 and that cell Cl- permeability is extremely low. In frog retinal slices, Müller cell input resistance was 8.5 megohms when measured in the inner plexiform layer and 4.8 megohms when measured in the optic fiber layer. Intact, enzymatically dissociated salamander (Ambystoma tigrinum) cells had an input resistance of 7.9 megohms, whereas cells lacking their endfoot process (removed by surgical microdissection or by shearing force) had a resistance of 152 megohms. Pressure ejection of a 100 mM K+ solution near the proximal surface of the endfeet of dissociated salamander cells produced depolarizations 7 times greater than did ejections near the lateral face of the endfoot and 24 to 50 times greater than did ejections near other cell regions. Similar K+ ejection results were obtained from Müller cells in salamander and frog retinal slices. Taken together, these results demonstrate that in both the frog and the salamander, approximately 95% of the total membrane conductance of Müller cells is localized in the cell's endfoot process. In salamander, the specific membrane resistance of the endfoot membrane was estimated to be 32 ohm X cm2 whereas the specific resistance of the remainder of the cell was 7300 ohm X cm2. This remarkably nonuniform conductance distribution has important consequences for theories concerning K+ regulation in the retina and for mechanisms underlying electroretinogram generation.

Ambystoma↗
PubMed1984

2-Deoxyglucose labelling of the infrared sensory system in the rattlesnake, Crotalus viridis.

Infrared (IR) responsive nuclei in the rattlesnake Crotalus viridis were identified by using 14C-2-deoxyglucose (2DG) and autoradiography. Following 2DG intracardial injection, the IR-sensitive pit organ was stimulated periodically with an IR stimulus for 5 hours. The nucleus of the lateral descending trigeminal tract (LTTD, the primary IR sensory nucleus) was labelled heavily with 2DG. Labelling was bilateral, but somewhat heavier ipsilateral to the stimulated pit organ. The nucleus reticularis caloris (RC, the secondary nucleus of the IR system) was lightly labelled ipsilaterally. The middle laminae of the contralateral optic tectum (which contain IR-responsive units) were distinctly labelled; the corresponding layers of the ipsilateral tectum were lightly labelled. A subcerebellar nucleus not known to be part of the IR system was heavily labelled bilaterally. No consistent labelling was found in the diencephalon or telencephalon. Since units in the LTTD do not respond to stimulation of the contralateral pit yet the LTTD is labelled with 2DG when there is contralateral pit stimulation, several controls were carried out. Unilateral injection of 3H-proline into LTTD revealed no projection to the contralateral LTTD. In a monocularly, visually stimulated animal with both pits occluded, the LTTD still showed heavy but equal 2DG labelling bilaterally. In addition, the outer layers of the contralateral optic tectum were heavily labelled. No 2DG labelling of the LTTD was obtained when branches of the trigeminal nerve innervating the LTTD were previously cut. These results suggest that much of the 2DG labelling in the LTTD is due to spontaneous ongoing activity from the pit organ rather than from IR evoked activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Control of extracellular potassium levels by retinal glial cell K+ siphoning.

Efflux of K+ from dissociated salamander Müller cells was measured with ion-selective microelectrodes. When the distal end of an isolated cell was exposed to high concentrations of extracellular K+, efflux occurred primarily from the endfoot, a cell process previously shown to contain most of the K+ conductance of the cell membrane. Computer simulations of K+ dynamics in the retina indicate that shunting ions through the Müller cell endfoot process is more effective in clearing local increases in extracellular K+ from the retina than is diffusion through extracellular space.

Ambystoma↗
PubMed1984

Model of electroretinogram b-wave generation: a test of the K+ hypothesis.

Generation of the electroretinogram b-wave is simulated with a computer model representing a dark-adapted amphibian retina. The simulation tests the K+ hypothesis of b-wave generation, which holds that b-wave currents arise from localized Müller cell depolarizations generated by light-evoked increases in extracellular K+ concentration, [K+]o. The model incorporates the following components and processes quantitatively: 1) two time-dependent K+ sources representing the light-evoked [K+]o increases in the inner and outer plexiform layers, 2) a time- and [K+]o-dependent K+ sink representing the [K+]o decrease in the rod inner segment layer, 3) diffusion of released K+ through extracellular space, 4) active K+ reuptake and passive K+ drift across the Müller cell membrane, 5) spatial variations in the tortuosity factor and the volume fraction of extracellular space, 6) an extraretinal shunt resistance. Müller cells are modeled with 1) cytoplasmic resistance, 2) spatial variations in membrane permeability to K+, and 3) a membrane potential specified by the Nernst equation and transmembrane current flow. For specified K+ source and sink densities, the model computes [K+]o variations in time and retinal depth. Based on these [K+]o distributions, Müller cell potentials, current source-density profiles, and intraretinal and transretinal voltages are calculated. Imposed [K+]o distributions similar to those seen experimentally during the b-wave lead to the generation of a transient b-wave response and to a prolonged Müller response in the model system. These response time courses arise because the b-wave is dominated by the short-lived distal [K+]o increase, while the Müller response primarily reflects the long-lived proximal [K+]o increase. Current source-density distributions and intraretinal voltage profiles that are generated by the model at the peak of the b-wave closely resemble experimental results. The model generates a realistic slow PIII potential in response to prolonged [K+]o decreases in the distal retina and reproduces the K+ ejection results of Yanagida and Tomita (50) accurately. Simulations also suggest that tissue damage caused by K+-selective micropipettes in experimental preparations can lead to an underestimation of the distal [K+]o increase. The simulations demonstrate that the spatiotemporal properties of intraretinal b-wave voltages and currents and Müller cell responses can be generated according to the K+ hypothesis: by passive Müller cell depolarization driven by variations in [K+]o.

Animals↗
PubMed1981

Integration of visual and infrared information in bimodal neurons in the rattlesnake optic tectum.

Bimodal neurons in the rattlesnake tectum, which receive sensory input from the retina and from the infrared-sensing pit organ, exhibit novel, highly nonlinear cross-modality interactions. Some units respond only to simultaneous bimodal stimulation. Others respond to only one of the two modalities, but show greatly enhanced or depressed responses when stimulated simultaneously in the second modality. These cross-modality interactions may play an important role in recognizing and orienting toward biologically important objects.

Action Potentials↗