PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Retinal Horizontal Cells”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed1998

Ca2+ regulation by the Na(+)-Ca2+ exchanger in retinal horizontal cells depolarized by L-glutamate.

This study is concerned with regulation of the intracellular Ca2+ concentration ([Ca2+]i) of horizontal cells isolated from cyprinid fish retinae, with the main emphasis on the role of the (Na+)-Ca2+ exchanger. An inward current was blocked by Ca2+ (4 mM) during prolonged (> 1 h) depolarization by L-glutamate (100 microM) in the whole-cell voltage-clamp configuration, suggesting the persistent activation of voltage-gated Ca2+ channels. This (Co2+)-sensitive current was absent when extracellular Na+ was replaced by Li+ to suppress (Na+)-Ca2+ exchange. Measurement of [Ca2+]i using the Fura-2 ratiometric method gave the following results. (1) L-Glutamate (100 microM) caused [Ca2+]i to increase from the resting level of 75.4+/-36.8 nM (mean +/-S.D., n = 11) to the maximum level (2.2+/-1.4 microM, n = 11) within 15 s and then to decrease to a steady level of 0.59+/-0.23 microM (n = 11). (2) Nifedipine (100 microM) lowered the L-glutamate-induced steady [Ca2+]i level, which was still higher than the resting level. (3) L-Glutamate caused [Ca2+]i to increase even after blockading the voltage-gated Ca2+ channels by nifedipine or by clamping the membrane voltage at -55 mV. (4) (Na+)-free superfusate elevated the L-glutamate-induced steady [Ca2+]i level. (5) The time course of the [Ca2+]i decrease from the L-glutamate-induced steady level to the resting level was prolonged in the (Na+)-free superfusate. These results suggest that the (Na+)-Ca2+ exchanger extrudes intracellular Ca2+ to maintain a low [Ca2+]i level by counteracting the continuous Ca2+ influx through the voltage-gated Ca2+ channels and glutamate-gated channels when horizontal cells in situ are tonically depolarized by L-glutamate released from the photoreceptors. The (Na+)-Ca2+ exchange current isolated by a voltage-clamp experiment depends exponentially on the membrane potential.

Animals↗
PubMedDate not supplied

Evidence for calcium/calmodulin dependence of spinule retraction in retinal horizontal cells.

Horizontal cells of the carp retina alter their synaptic connections with cones during dark and light adaptation. At light onset, dendrites of horizontal cells, which are positioned laterally at the ribbon synapse, form "spinules," little processes with membrane densities. Spinules are retracted again during dark adaptation. Spinule retraction is also elicited upon glutamate application to the retina. In the present study, we address the question whether calcium/calmodulin-dependent pathways are involved in dark- and glutamate-evoked spinule retraction. Light-adapted retinas were isolated and subsequently dark adapted during incubation in media of different calcium concentrations. Spinule retraction was clearly blocked in low-calcium solutions (5 microM and 50 nM CaCl2). Incubation in medium containing cobalt chloride (2 mM) had the same effect. Both treatments blocked the glutamate-induced spinule retraction as well. These results indicate that spinule retraction is induced by a calcium influx into horizontal cells. To investigate whether calmodulin, the primary calcium receptor in eukaryotic cells, is present at the site of spinule formation, light- and dark-adapted retinas, embedded in LR White resin, were labelled with an antibody against calmodulin and gold-conjugated secondary antibodies. Horizontal cell dendrites at the ribbon synapse revealed strong calmodulin immunoreactivity, which was more than twice as high in light- as in dark-adapted retinas. The incubation of isolated retinas with the calmodulin antagonists W5 and W13 inhibited spinule retraction. In summary, these results suggest that spinule retraction may be regulated by calcium influx into horizontal cells and subsequent calcium/calmodulin-dependent pathways.

Animals↗
PubMedDate not supplied

Calcium-induced calcium release and calcium buffering in retinal horizontal cells.

Calcium plays an integral role in intracellular signaling and process control in neurons. In the outer retina, it is a key component to the phototransduction cycle and neurotransmitter release in photoreceptor and bipolar cell terminals. It also contributes to the responses of horizontal and bipolar cells. In the dark, horizontal cells are depolarized and calcium enters via calcium permeant AMPA receptors and voltage-activated calcium channels. As a result, horizontal cells must be capable of handling high calcium loads without sustaining damage. The aim of this study was to examine the components determining the intracellular calcium levels in H2 horizontal cells in the retina of white bass. Calcium responses were evoked in isolated cells by depolarizing voltage steps and monitored by conventional imaging techniques. The responses consisted of two components: calcium entry through voltage-gated calcium channels and subsequent release from intracellular stores by calcium-induced calcium release (CICR). Under control conditions, changes in calcium levels reached 541 nM on average from a basal level of 60 nM. When release from CICR stores was blocked with ryanodine or dantrolene, calcium levels barely reached 180 nM. The threshold level needed to trigger CICR was dependent on the duration of the applied depolarization and increased in response to shorter pulses. In studies of temporal integration, cells were depolarized to 0 mVs for increasing periods of time. In the absence of CICR, the responses grew exponentially with time and saturated at approximately 200 nM in response to pulses of 8 s or longer. CICR extended the range of temporal integration to 20 s and the saturating maximum rose to 600 nM. Our results indicate that the slow time-course of the responses, the relatively small changes in intracellular calcium, and the contribution of CICR are shaped by the activity of strong calcium-removal mechanisms and an unusually large calcium-buffering ratio estimated to be over 2,500.

Animals↗
PubMedDate not supplied

Glutamate receptor subtypes in human retinal horizontal cells.

Glutamate receptor currents were examined in horizontal cells from cultured human retina using whole-cell recording procedures. Horizontal cells possess both AMPA and kainate receptors and both produce significant sustained currents. The kainate-induced current did not show significant desensitization and was not enhanced by concanavalin A. The sustained AMPA current was smaller than the kainate current, but the difference was almost entirely due to pronounced desensitization. The horizontal cell AMPA current was enhanced by cyclothiazide but not by PEPA, indicating the presence of the flip receptor variant. GYKI-52466 blocked the AMPA response (IC50 = 5 microM against 100 microM AMPA) but also blocked the kainate response (IC50 = 45 microM against 100 microM kainate). The diversity of glutamate receptors in human horizontal cells suggests that synaptic input to these neurons may be multiplexed through both kainate and AMPA channels.

Benzodiazepines↗
PubMedDate not supplied

Electrical coupling of retinal horizontal cells mediated by distinct voltage-independent junctions.

Electrical coupling between H2 horizontal cell pairs isolated from the hybrid bass retina was studied using dual whole-cell, voltage-clamp technique. Voltage-dependent inactivation of junctional currents in response to steps in transjunctional voltage (Vj) over a range of +/-100 mV was characterized for 89 cell pairs. Approximately one-quarter of the pairs exhibited strongly voltage-dependent junctions (>50% reduction in junctional current at +/-100 mV), another quarter of the pairs exhibited voltage-independent junctional current (<5% reduction at +/-100 mV), and the remainder of the pairs exhibited intermediate values for voltage inactivation. We focused on further characterizing the Vj-independent junctions of horizontal cells, which have not been described previously in detail. When Lucifer Yellow dye was included in one recording pipette, pairs exhibiting Vj-independent coupling showed no (9/12), or limited (3/12), passage of dye. Vj-independent coupling was markedly less sensitive to the modulators SNP (100-300 microM, -9% reduction in coupling) and dopamine (100-300 microM, -6%) than were Vj-dependent junctions (-45% and -44%). However, simultaneous application of both SNP and dopamine significantly reduced Vj-independent coupling (-56%). Both Vj-independent and Vj-dependent junctions were blocked by DMSO (1-2%), but Vj-independent junctions were not blocked by heptanol. Single-channel junctional conductances of Vj-independent junctions range from 112-180 pS, versus 50-60 pS for Vj-dependent junctions. The results reveal that Vj-independent coupling in a subpopulation of horizontal cells from the hybrid bass retina is mediated by cellular junctions with physiological and pharmacological characteristics distinct from those previously described in fish horizontal cells.

Animals↗
PubMedDate not supplied

Dopamine enhances excitatory amino acid-gated conductances in cultured retinal horizontal cells.

In the teleost retina, cone horizontal cells receive extensive innervation from dopaminergic interplexiform cells, and possess dopamine receptors whose activation stimulates adenylate cyclase. Exogenously applied dopamine modifies several aspects of horizontal cell activity in the intact retina, including the responsiveness of these neurons to light and the strength of electrical coupling between them. We have used whole-cell voltage clamp methods to examine whether dopamine can alter the light-responsiveness of horizontal cells by changing their sensitivity to the neurotransmitter released by the photoreceptors. We report that dopamine and cyclic AMP, although having little direct effect on resting membrane conductance, greatly enhance ionic conductances gated by kainate, an agonist of the transmitter released by the photoreceptors, and by L-glutamate, the agent proposed to be the photoreceptor transmitter. Our results provide the first direct evidence for dopaminergic regulation of excitatory amino-acid neurotransmission in the vertebrate nervous system and suggest a possible mechanism to explain the reduction in the responsiveness of horizontal cells observed when retinas are treated with dopamine.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

AMPA-preferring receptors with high Ca2+ permeability mediate dendritic plasticity of retinal horizontal cells.

The synaptic complex formed by the cone photoreceptor pedicles and the dendrites of horizontal cells in the teleost retina undergoes structural changes during light adaptation. Numerous spinules are formed by the terminal dendrites, and they are subsequently retracted during dark adaptation. In a retina kept under continuous illumination, the retraction process can be initiated by analogues of the neurotransmitter glutamate acting at AMPA/kainate receptors. On the other hand, the retraction process depends on calcium influx and the subsequent activation of CaMkII. We show here that the retraction of spinules induced by AMPA or kainate is not impaired in the presence of cobalt, making an involvement of voltage-gated calcium channels unlikely. Using calcium imaging techniques with isolated horizontal cells, we demonstrate that AMPA and kainate, but not NMDA, increase [Ca2+]i in the presence of nicardipine, caffeine and thapsigargin. The increase of [Ca2+]i under these conditions depends on [Ca2+]o and on the agonist in a dose-dependent manner, suggesting that the increase of [Ca2+]i is largely due to calcium influx through the agonist-gated channel. Pharmacological studies were performed to determine whether AMPA- and/or kainate-preferring receptors mediate the calcium influx. The AMPA-preferring receptor antagonist LY303070 blocked glutamate- and kainate-evoked increases of [Ca2+]i in a concentration-dependent manner, indicating that kainate-preferring receptors contributed little or nothing to the observed [Ca2+]i increase. This was supported by experiments where cyclothiazide (which blocks the desensitization of AMPA receptors) and concanavalin A (which potentiates responses mediated by kainate receptors) were applied. In all cases, LY303070 blocked the agonist-evoked increase of [Ca2+]i. The presence of AMPA-preferring receptors with high Ca2+ permeability on horizontal cells was also supported by measuring agonist-induced currents using whole-cell recording techniques. Furthermore, LY303070 was able to impair the retraction of spinules during dark adaption in the in vivo situation.

Animals↗
PubMed1985

Dopamine decreases conductance of the electrical junctions between cultured retinal horizontal cells.

Horizontal cells from the white perch were isolated by enzymatic treatment and trituration of the retina and were maintained in culture for 1-5 days. Overlapping pairs of horizontal cells were identified, and the two cells were recorded from simultaneously, using whole-cell patch clamp techniques. Electrical coupling between cells was determined by passing current pulses into one cell, the driver cell, while (i) recording voltage changes in the other, follower cell, or (ii) measuring current flow into the follower cell. Most cell pairs of the same morphological type were coupled electrically, with coupling coefficients often greater than 0.9. Junctional resistance was typically found to be between 20 and 60 M omega and junctional conductance was between 150 and 500 nS. After application of 1-microliter pulses of dopamine (200 microM) to coupled pairs of cells, the coupling coefficient fell to approximately equal to 0.1, junctional resistance increased to 300-700 M omega, and junctional conductance decreased to 15-30 nS. Recovery of coupling took, for most cell pairs tested, 8-15 min after dopamine application. The exogenous application of 8-bromo-cyclic AMP (0.5-1 mM) also caused uncoupling of horizontal cell pairs; however, neither isoprenaline nor L-glutamate altered coupling significantly.

Animals↗
PubMed1987

Retinal horizontal cell gap junctional conductance is modulated by dopamine through a cyclic AMP-dependent protein kinase.

The action of many neuromodulators is mediated by intracellular second messengers such as cyclic AMP. In the retina, exogenously applied dopamine alters the conductance of gap junctions between cultured horizontal cells and this effect is mediated by cyclic AMP. However, it is not known how cyclic AMP modulates horizontal cell gap junction function. Here I report that cyclic AMP works by way of a cyclic AMP-dependent protein kinase. Cyclic AMP-dependent protein kinase injected into coupled horizontal cells from white bass (Roccus chrysops) rapidly and reversibly uncoupled the cells, mimicking the actions of dopamine. The threshold for the effect was between 0.06 and 0.03 microM. Injection of Walsh inhibitor of protein kinase [Walsh, D. A., Ashby, C. D., Gonzalez, C., Calkins, D., Fischer, E. H. & Krebs, E. G. (1971) J. Biol. Chem. 246, 1977-1985] blocked the effect of dopamine. Thus, the action of dopamine is to raise intracellular levels of cyclic AMP, which then activates a cyclic AMP-dependent protein kinase. Although not tested, it is likely that the cyclic AMP-dependent protein kinase phosphorylates a protein, possibly a gap junction protein, to alter conductance.

Animals↗
PubMed1990

Effects of gamma-aminobutyric acid on skate retinal horizontal cells: evidence for an electrogenic uptake mechanism.

In the retinae of many vertebrates, there are classes of horizontal cell that probably utilize gamma-aminobutyric acid (GABA) as a neurotransmitter. As with other amino acid transmitter agents, the postsynaptic action of GABA is thought to be terminated by uptake into neurons and glia surrounding the release site. The present study examined whether an uptake system for GABA could be detected in isolated skate horizontal cells by means of electrophysiological methods. Pressure ejection of GABA onto voltage-clamped horizontal cells produced an inward current that showed no sign of desensitization regardless of the GABA concentration. The dose-response relationship followed simple Michaelis-Menten kinetics, with a half-maximal response elicited at approximately 110 microM. Nipecotic acid produced a similar current and reduced the responses to GABA when introduced in the bath solution prior to the GABA pulse. On the other hand, application of 500 microM muscimol or 1 mM baclofen, GABAA and GABAB receptor agonists, respectively, were completely without effect. The GABA-induced current was not blocked by superfusion with 500 microM bicuculline, 500 microM picrotoxin, or 500 microM phaclofen. However, the responses to GABA were abolished when the cells were superfused in Ringer's solution in which choline or lithium had been substituted for sodium, and were reduced when the extracellular chloride concentration was decreased from 266 mM to 16 mM. Current-voltage data showed a maximal response to GABA when the cells were held at or below their resting potential. At more depolarized levels, the inward current became progressively smaller until, near +50 mV, it could no longer be detected; over the range tested (-90 to +50 mV), the response never reversed into an outward current. These findings suggest that the GABA-induced currents in skate horizontal cells are mediated by an electrogenic uptake mechanism.

Animals↗
PubMed1990

Dopamine induces neurite retraction in retinal horizontal cells via diacylglycerol and protein kinase C.

Dopamine causes a significant retraction of neurites of bull-head catfish horizontal cells maintained in culture. The effects of dopamine are blocked by haloperidol and SCH 23390, a D1 antagonist, but not by sulpiride, a D2 antagonist. The dopamine-induced morphological changes were mimicked by SKF 38393, a D1 agonist, but not by quinpirole, a D2 agonist. Kainate also caused process retraction, but other neuroactive substances tested including glutamate, 5-hydroxytryptamine, N-methyl-D-aspartate, gamma-aminobutyric acid, and glycine caused only minor changes in neurite length. Cyclic AMP analogues do not induce neurite retraction in horizontal cells, indicating that this effect of dopamine is not mediated by cyclic AMP. However, a protein kinase C activator (phorbol 12-myristate 13-acetate) and synthetic diacylglycerol analogs (1-oleoyl-2-acetyl-sn-glycerol and dioctanoglycerol) caused marked neurite retraction. Their effects, as well as the dopamine-induced changes, were blocked by staurosporine, a potent protein kinase antagonist. The results suggest that dopamine causes neurite retraction by the activation of protein kinase C via diacylglycerol.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Activation of a D2 receptor increases electrical coupling between retinal horizontal cells by inhibiting dopamine release.

In the fish retina, interplexiform cells release dopamine onto cone-driven horizontal cells. Dopamine decreases the electrical coupling between horizontal cells by activating adenylate cyclase through dopamine D1 receptors. Using intracellular recording, we have studied the effect of dopamine D2 receptor activation on horizontal cell electrical coupling in the intact goldfish retina. Superfusion of the D2 agonist LY171555 (quinpirole; 0.2-10 microM) increased horizontal cell coupling, as indicated by a decrease in responses to centered spots or slits of light. The length constant of the horizontal cell network increased an average of 31%. Although dopamine (0.5-20 microM) uncoupled horizontal cells, lower concentrations (e.g., 0.2 microM) initially uncoupled and then subsequently increased coupling beyond initial control levels. The coupling effect of LY171555 (10 microM) was blocked completely by prior application of the D1 agonist SKF 38393 at saturating (20 microM) or nonsaturating (2.5-5.0 microM) doses. Prior treatment of the retinas with 6-hydroxydopamine, which destroyed dopaminergic neurons, eliminated the coupling effect of LY171555 but not the uncoupling effect of SKF 38393. These results suggest that goldfish horizontal cells contain D1, but not D2, receptors and that dopamine activation of D2 autoreceptors on interplexiform cells inhibits dopamine release onto horizontal cells so that the electrical coupling between horizontal cells increases.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Ionotropic non-N-methyl-D-aspartate agonists induce retraction of dendritic spinules from retinal horizontal cells.

Horizontal cells invaginate the photoreceptors in the retina and form reciprocal synaptic connections in the cone pedicles. In fish retina the pattern of synaptic connections is plastic and modulated by the ambient light conditions. Numerous dendritic spinules protrude from the terminal horizontal-cell dendrites into the cone pedicle when the retina is light-adapted and are retracted during dark adaptation. The retraction of spinules can be induced during maintained illumination by an injection of the putative cone transmitter L-glutamate or its analogue kainic acid into the vitreous humor. The formation and the retraction of spinules have a time course of minutes. Activation of protein kinase C through phorbol esters initiates the formation of spinules, but the retraction has not yet been linked to a specific second messenger. Herein we report that physiological concentrations of the glutamate analogs quisqualic acid and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid induce retraction of spinules during maintained illumination. (+/-)-trans-1-Amino-1,3-cyclopentanedicarboxylic acid, an agonist for the metabotropic quisqualic acid receptor, was without effect on spinule retraction. N-Methyl-D-aspartate and L-2-amino-4-phosphonobutyric acid, agonists at other types of glutamate receptors, were also without any effect. The effects of the active agonists persisted when synaptic transmission was blocked. In the presence of the ionotropic quisqualate receptor antagonist 6-cyclo-7-nitro-quinoxaline-2,3-dione the effects of all active agonists were blocked. These results demonstrate that activation of ionotropic quisqualate receptors on the horizontal-cell membrane can induce dendritic spinule retraction, a process associated with dark adaptation.

Aminobutyrates↗
PubMed1994

Dopamine alters glutamate receptor desensitization in retinal horizontal cells of the perch (Perca fluviatilis).

The patch-clamp technique in combination with a fast liquid filament application system was used to study the effect of dopamine on the glutamate receptor desensitization in horizontal cells of the perch (Perca fluviatilis). Kinetics of ligand-gated ion channels in fish horizontal cells are modulated by dopamine. This modulation is presumably mediated by a cAMP-dependent protein phosphorylation. Before incubation with dopamine, the glutamate receptors of horizontal cells activate and desensitize with fast time constants. In the whole-cell recording mode, fast application of the agonists L-glutamate, quisqualate, or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid prior to the dopamine incubation gives rise to fast transient currents with peak values of about 200 pA that desensitize within 100 ms. Kainate as agonist produced higher steady-state currents but no transient currents. After incubation of the cells with dopamine for 3 min, the desensitization was significantly reduced and the agonists L-glutamate, quisqualate, or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid induced steady-state currents with amplitudes that were similar to the previously observed transient currents. Kainate-induced currents were only slightly affected. Fast desensitizing currents upon fast application of L-glutamate were also recorded from outside-out patches that were excised from horizontal cells before incubation with dopamine. The currents from excised patches desensitized to a steady-state level of about 0.2 of the peak amplitude with time constants of less than 2 ms. When the outside-out patches were excised from cells after dopamine incubation, steady-state currents were enhanced and no transient currents were observed. The results may indicate that the dopamine-dependent modulation of glutamate-induced currents, which is presumably mediated by a protein phosphorylation, is due to an alteration of the desensitization of the glutamate receptors.

Animals↗
PubMed1994

Arachidonic acid blocks gap junctions between retinal horizontal cells.

Horizontal cells in turtle retinae are electrically coupled via gap junctions, and the input resistances of the cells are too low to be measured. However, intracellular injection of arachidonic acid into horizontal cells caused great increases in the input resistances of the cells, and the cells could be easily polarized by intracellular current injection. The injection of arachidonic acid also caused decrease in light responses of horizontal cells to surround illumination, and blocked dye-couplings with Lucifer Yellow CH. On the other hand, injection of a lipoxygenase inhibitor or a guanylate cyclase inhibitor into horizontal cells suppressed the decoupling effect of arachidonic acid. These findings suggest that lipoxygenase metabolites of arachidonic acid block gap junctions by activating guanylate cyclase.

Animals↗
PubMed1996

Kainic acid blocks a TTX-sensitive sodium channel in retinal horizontal cells of the turtle (Pseudemys scripta elegans).

The aim of this study was to investigate the effects of excitatory amino acids on channels found in horizontal cell membranes using patch-clamp techniques. We unexpectedly found that the excitatory amino acid receptor agonist, kainic acid, reversibly inhibited the transient tetrodotoxin (TTX)-sensitive Na+ current in isolated horizontal cell bodies and axons from the retina of the turtle (Pseudemys scripta elegans). The effect of kainic acid was antagonized by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. Kainic acid activated a non-selective cation current, a finding that was consistent with previous reports, and which would account for the kainate induced depolarisation of these cells. The inhibition of the transient TTX-sensitive Na+ current by kainic acid might be important in the modification of the kinetics of responses to excitatory amino acid analogues often observed during intracellular recording from these cells.

Animals↗
PubMed2004

Role of Ca2+ store in AMPA-triggered Ca2+ dynamics in retinal horizontal cells.

Fura-2 fluorescent calcium imaging was applied to measure [Ca(2+)](i) in freshly dissociated horizontal cells of carp retina, and a model containing endoplasmic reticulum (ER) membrane processes and plasma membrane processes was constructed for quantitative analyses of the AMPA-triggered calcium dynamics. A transient increase followed by a sustained steady level of [Ca(2+)](i) was observed when 100 microM AMPA was applied, while the initial transient increase of [Ca(2+)](i) was suppressed by exogenously applied ryanodine. The model analyses results suggest that the AMPA-triggered calcium dynamics involves a number of cytoplasmic and endoplasmic processes that interact with each other. It also suggests that calcium store is an important part contributing to the transient calcium signal.

Animals↗