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At least 19 recordsLinked to original sources
PubMed1989

Localization of L-glutamic acid decarboxylase mRNA in cat retinal horizontal cells by in situ hybridization.

Retinal horizontal cells receive synaptic input from photoreceptors and provide a pathway for lateral interactions in the vertebrate retina. In nonmammalian retinas, the H1 horizontal cells appear to use gamma-amino butyric acid (GABA) as their neurotransmitter. The transmitter used by mammalian horizontal cells, however, remains to be identified. In the present study, we have employed in situ hybridization to examine whether cat retinal horizontal cells contain L-glutamic acid decarboxylase (GAD) mRNA and hence might use GABA as their transmitter. In the cat retina, labeled cell bodies were found in the inner nuclear layer and the ganglion cell layer. No labeled cells were found in the photoreceptor layer. In the inner nuclear layer, labeled somata were present at two locations. The majority of them (approximately 72%) were located in the vitread side of the inner nuclear layer bordering the inner nuclear layer/inner plexiform layer boundary. A second class of labeled cells in the inner nuclear layer (approximately 20%) had larger somata and were present at the inner nuclear layer/outer plexiform layer boundary. Double labeling experiments with antisera to parvalbumin, a horizontal cell marker, showed that these perikarya belonged to horizontal cells. RNA blot analysis showed that cat retina contains a single species of GAD mRNA that is about 4 kb in size. These data show that in addition to GABAergic amacrine, displaced amacrine, and interplexiform cells described previously, horizontal cells contain GAD mRNA and may use GABA as their neurotransmitter. Hence, GABA may be a transmitter that is involved in lateral inhibition in both nonmammalian and mammalian retinas.

Animals↗
PubMed1993

Dopamine modulates in a differential fashion T- and L-type calcium currents in bass retinal horizontal cells.

White bass (Roccus chrysops) retinal horizontal cells possess two types of voltage-activated calcium currents which have recently been characterized with regard to their voltage dependence and pharmacology (Sullivan, J., and E. M. Lasater. 1992. Journal of General Physiology. 99:85-107). A low voltage-activated transient current was identified which resembles the T-type calcium current described in a number of other preparations, along with a sustained high threshold, long-lasting calcium current that resembles the L-type calcium current. Here we report on the modulation of horizontal cell calcium channels by dopamine. Under whole-cell voltage clamp conditions favoring the expression of both calcium currents, dopamine had opposing actions on the two types of voltage-sensitive calcium currents in the same cone-type horizontal cell. The L-type calcium current was significantly potentiated by dopamine while the T-type current was simultaneously reduced. Dopamine had no effect on calcium currents in rod-type horizontal cells. Both of dopamine's actions were mimicked with the D1 receptor agonist, SKF 38393, and blocked by application of the D1 specific antagonist, SCH 23390. Dopamine's actions on the two types of calcium currents in white bass horizontal cells are mimicked by the cell membrane-permeant cyclic AMP derivative, 8-(4-chlorophenylthio)-cyclic AMP, suggesting that dopamine's action is linked to a cAMP-mediated second messenger system. Furthermore, the inhibitor of cAMP-dependent protein kinase blocked both of dopamine's actions on the voltage-dependent calcium channels when introduced through the patch pipette. This indicates that protein phosphorylation is involved in modulating horizontal cell calcium channels by dopamine. Taken together, these results show that dopamine has differential effects on the voltage-dependent calcium currents in retinal horizontal cells. The modulation of these currents may play a role in shaping the response properties of horizontal cells.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2000

Ionic current model of rabbit retinal horizontal cell.

We propose a mathematical model of rabbit retinal horizontal cell based on the ionic current mechanisms. Five types of ionic currents in rabbit retinal horizontal cell, I(Na), I(Ca), I(Kv), I(A) and I(Ka), are described by Hodgkin-Huxley type equations based on voltage clamp measurements. In simulation the model reproduced similar responses to voltage and current clamp experiments. Under the current clamp experiment a repetitive action potential was found on A-type rabbit horizontal cells. Our result suggests that the repetitive action potential is generated by an interaction Of I(Ca) and I(Kv).

Action Potentials↗
PubMed1982

Hyperpolarization of retinal horizontal cells by excitatory amino acid neurotransmitter antagonists.

Membrane potentials of retinal horizontal cells have been recorded fro isolated fish retinae perfused with Ringer solutions containing various drugs. We show that glutamate diethyl ester (GDEE) and gamma-D-glutamylglycine (DGG), respectively antagonists of the excitatory neurotransmitter agonists quisqualate and kainate, hyperpolarize horizontal cells and, at mM concentrations, suppress the light evoked S-potentials. They were not, however, generally effective in blocking the depolarizing effects of exogenous kainate and quisqualate, but in the 10% of the experiments where they were effective GDEE blocked selectively quisqualate binding the DGG blocked selectively kainate binding. In contrast, folic acid consistently hyperpolarized the horizontal cells and at mM concentrations, blocked partially the effects of kainate and quisqualate. These results are consistent with the depolarizing actions of kainate and quisqualate on retinal horizontal cells [9, 10], but the inconsistent blocking of kainate and quisqualate effects by DGG and GDEE seriously restricts their value as a tool in retinal neurophysiology.

Animals↗
PubMed1990

Dopamine modulates the kinetics of ion channels gated by excitatory amino acids in retinal horizontal cells.

Upon exposure to dopamine, cultured teleost retinal horizontal cells become more responsive to the putative photoreceptor neurotransmitter L-glutamate and to its analog kainate. We have recorded unitary and whole-cell currents to determine the mechanism by which dopamine enhances ion channels activated by these agents. In single-channel recordings from cell-attached patches with agonist in the patch pipette, the frequency of 5- to 10-pS unitary events, but not their amplitude, increased by as much as 150% after application of dopamine to the rest of the cell. The duration of channel openings also increased somewhat, by 20-30%. In whole-cell experiments, agonists with and without dopamine were applied to voltage-clamped horizontal cells by slow superfusion. Analysis of whole-cell current variance as a function of mean current indicated that dopamine increased the probability of channel opening for a give agonist concentration without changing the amount of current passed by an individual channel. For kainate, noise analysis additionally demonstrated that dopamine did not alter the number of functional channels. Dopamine also increased a slow spectral component of whole-cell currents elicited by kainate or glutamate, suggesting a change in the open-time kinetics of the channels. This effect was more pronounced for currents induced by glutamate than for those induced by kainate. We conclude that dopamine potentiates the activity of horizontal cell glutamate receptors by altering the kinetics of the ion channel to favor the open state.

Analysis of Variance↗
PubMed2006

Cadherin is required for dendritic morphogenesis and synaptic terminal organization of retinal horizontal cells.

Dendrite morphology of neurons provides a structural basis for their physiological characteristics, and is precisely regulated in a cell type-dependent manner. Using a unique transposon-mediated gene transfer system that enables conditional and cell-type specific expression of exogenous genes, we investigated the role of cadherin on dendritic morphogenesis of horizontal cells in the developing chicken retina. We first visualized single horizontal cells by overexpressing membrane-targeted EGFP, and confirmed that there were three subtypes of horizontal cells, the dendritic terminals of which projected to distinct synaptic sites in the outer plexiform layer. Expression of a dominant-negative cadherin decreased the dendritic field size, and perturbed the termination of dendritic processes onto the photoreceptor cells. The cadherin blockade also impaired the accumulation of GluR4, a postsynaptic marker, at the cone pedicles. We thus provide in vivo evidence that cadherin is required for dendrite morphogenesis of horizontal cells and subsequent synapse formation with photoreceptor cells in the vertebrate retina.

Animals↗
PubMedDate not supplied

Asymmetrical dynamics of voltage spread in retinal horizontal cell networks.

Lateral voltage spread in electrically coupled retinal horizontal cell networks is the substrate of center-surround antagonism in bipolar and ganglion cells. We studied its spatial and temporal properties in more detail in turtle L1 horizontal cells by using a contrast border as light stimulus. Experimental data were contrasted with expectations from a linear continuum model to specify the impact of nonlinearities. The assumptions for the diffusion term of the continuum model were justified by neurobiotin labeling. Measured voltage spread revealed two different length constants lambda+ and lambda0, under illuminated and nonilluminated regions of the retina, respectively, as predicted by the linear model. Length constants in the illuminated region showed strong temporal dynamics. For the initial phase of the horizontal cell responses lambda+ was larger than lambda0. This was also in accordance with the model. Right at the peak of the response, however, lambda+ dropped below lambda0 and did not change any more. It is this temporal reversal of asymmetry in voltage spread and not the decrease of lambda+ itself that is lacked by the linear model. The observed independence of the mean ratio lambda+/lambda0 from light intensity in both the peak and the plateau phases of horizontal cell responses contradicts the linear assumption, too. These two effects have to be addressed to local nonlinearities in the horizontal cell network like a negative feedback loop from photoreceptors and/or voltage-dependent conductances. Due to the failure of the linear model, firm conclusions about the membrane resistance and the coupling resistance of the horizontal cell network cannot be drawn from length constant measurements.

Animals↗
PubMed1993

Depolarization elicits, while hyperpolarization blocks uptake of endogenous glutamate by retinal horizontal cells of the turtle.

We have employed an immunoreaction against glutamate to qualitatively demonstrate varying levels of glutamate in retinal horizontal cells of the turtle. Glutamate-like immunoreactivity (GLI) in horizontal cells could be demonstrated after glutamate decarboxylase was inhibited by aminooxyacetic acid (AOAA) and its degradation to GABA was blocked. Depolarization of horizontal cells by kainic acid (KA) induces strong glutamate immunoreactivity in these cells, whereas hyperpolarization by 2,3-cis piperidine dicarboxylate (PDA) abolishes glutamate-like immunoreactivity in horizontal cells. When glutamate release from cones and bipolar cells is blocked in the absence of calcium, or when glutamate uptake is blocked by DL-threo beta-hydroxy aspartate, KA/AOAA treatment of the retina does not induce GLI in horizontal cells. Our data show that horizontal cells are capable of taking up glutamate from the endogenous retinal pool in an activity dependent way. Our interpretation of these findings is that retinal horizontal cells are capable of regulating glutamate levels in the extracellular space of the cone pedicle complex by an activity-dependent uptake system. We suggest that inhibition of glutamate uptake upon hyperpolarization rather than inhibition of GABA release may evoke the antagonistic surround response of retinal bipolar cells.

Aminooxyacetic Acid↗
PubMed1998

Spatio-temporal receptive fields in carp retinal horizontal cells.

1. The dynamics of the receptive fields of retinal horizontal cells were examined by applying a spatio-temporal modulated light signal to the retina. 2. The spatio-temporal receptive fields of both cone- and rod-driven horizontal cells, estimated through cross-correlation between the modulated light signal and the cells' responses, showed their receptive fields (the space-dependent component) to be reduced in size with time. 3. In cone-driven horizontal cells, the reduction in receptive field size was initially small but then rapidly became prominent with time. The time to peak of the time-dependent component of spatio-temporal receptive fields did not depend on the distance from the centre. 4. Application of a small amount of Co2+, an agent blocking the cone-driven horizontal cells' feedback action on cones, or GABA, resulted in a reversal of the time-dependent shrinkage of receptive fields to time-dependent expansion. 5. In rod-driven horizontal cells, the receptive field shrinkage was slow. The time to peak of the time-dependent component decreased with the distance from the centre. 6. Image processing experiments examining the response pattern in the horizontal cell layer (neural image) to a moving square of light showed smudging of the neural image when the time-dependent receptive field expansion was present, while there was essentially no smudging under conditions of receptive field shrinkage.

Animals↗
PubMed1996

Whole cell and single-channel properties of a unique voltage-activated sustained calcium current identified in teleost retinal horizontal cells.

1. A voltage-activated, sustained calcium current in white bass retinal cone horizontal cells was characterized on the basis of electrophysiological and pharmacological criteria. Studies were performed with the use of a combination of whole cell and single-channel analysis of outside-out excised patches from isolated, cultured retinal horizontal cells. 2. We found that the white bass sustained calcium channel represents a unique type of calcium channel. On the basis of our analysis, it does not fall into any current classification scheme. The horizontal cell channel shares some biophysical and pharmacological properties with the typical high-voltage-activated L-type channel, but it also has features in common with the P-type channel. 3. The biophysical characteristics of the channel were most typical of an L-type channel. It activated above -30 mV membrane potential and only very slowly inactivated. It had a single-channel conductance of 25 pS. 4. Like the typical L-type current, the horizontal cell current was sensitive to the dihydropyridine agonist Bay K 8644. It prolonged the channel open time, which resulted in a large increase in macroscopic current flow into the cell. However, unlike the typical L current, dihydropyridine antagonists (nifedipine, nimodipine, etc.) as well as the specific L-channel inhibitor diltiazem were only moderately effective at best. 5. In a previous study, we found the current was antagonized by a factor found in funnel-web spider toxin. Here we show that the current is completely blocked by low doses of omega-agatoxin IVA. These are characteristics of the P-type calcium channel. But unlike the P current, the horizontal cell current is relatively insensitive to low or high doses of omega-conotoxin MVIIC. 6. The overall combination of calcium channel characteristics sets apart the calcium channel in bass horizontal cells from previously described channels. It appears to be a unique, tissue-specific ion channel, which we have labeled the PL channel.

Animals↗
PubMedDate not supplied

Modulation of A-type potassium currents in retinal horizontal cells by extracellular calcium and zinc.

Extracellular Ca2+ and Zn2+ influence many aspects of retinal function. Here, we examined the effect of external Ca2+ and Zn2+ on potassium channels of retinal horizontal cells. When extracellular Ca2+ was lowered from 3 mM to 0.3 mM, horizontal cell transient outward currents elicited by voltage steps from resting membrane potential (-70 mV) were decreased by approximately 50%, whereas the sustained currents remained unchanged. This effect was due to a hyperpolarizing shift in the steady-state inactivation curve of A-type K+ currents when extracellular Ca2+ concentration was lowered. The mean half inactivation potential of the steady-state inactivation curves was hyperpolarized from -56.3 +/- 4.7 mV in 3 mM Ca2+ to -76.4 +/- 3.9 mV in 0.3 mM Ca2+. Neither the state-steady activation curve nor the kinetics of inactivation was significantly changed in low extracellular Ca2+. The addition of 30 microM Zn2+ restored peak outward currents in 0.3 mM Ca2+. The half inactivation voltages were depolarized from -70 +/- 2.8 mV in 0.3 mM Ca2+ to -56 +/- 2.6 mV in 0.3 mM Ca2+ plus 30 microM Zn2+. Taken together, the results indicate that external Ca2+ and Zn2+ maintain the activity of A-type potassium channels in retinal horizontal cells by influencing the voltage dependence of steady-state inactivation.

Animals↗
PubMed1984

Inositol incorporation into phosphoinositides in retinal horizontal cells of Xenopus laevis: enhancement by acetylcholine, inhibition by glycine.

The absorption of light by photoreceptor cells leads to an increased incorporation of [2-3H]inositol into phosphoinositides of horizontal cells in the retina of Xenopus laevis in vitro. We have identified several retinal neurotransmitters that are involved in regulating this response. Incubation with glycine, the neurotransmitter of an interplexiform cell that has direct synaptic input onto horizontal cells, abolishes the light effect. This inhibition is reversed by preincubation with strychnine. Acetylcholine added to the culture medium enhances the incorporation of [2-3H]inositol into phosphoinositides in horizontal cells when retinas are incubated in the dark. This effect is inhibited by preincubation with atropine. However, atropine alone does not inhibit the light-enhanced incorporation of [2-3H]inositol into phosphoinositides in the retina. gamma-Aminobutyric acid, the neurotransmitter of retinal horizontal cells in X. laevis, as well as dopamine and norepinephrine, have no effect on the incorporation of [2-3H]inositol into phosphoinositides. These studies demonstrate that the light-enhanced incorporation of [2-3H]inositol into phosphoinositides of retinal horizontal cells is regulated by specific neurotransmitters, and that there are probably several synaptic inputs into horizontal cells which control this process.

Acetylcholine↗
PubMed1987

Changes in response waveform of retinal horizontal cells during dark and light adaptation.

Changes in response waveform of retinal horizontal cells during dark and light adaptation were examined in the tiger salamander retina. In addition to sensitivity changes, the response waveform of HC was altered during visual adaptation: following bleaching or in the presence of background illumination, a transient depolarizing overshoot was observed at the cessation of the test flash. In contrast to the hyperpolarizing light responses, the depolarizing off-overshoots do not follow the standard threshold recovery time course during dark adaptation, neither do they obey Weber's law for increment thresholds during light adaptation. Simultaneous intracellular recordings from photoreceptors and HC revealed that the off-overshoot responses in light-adapted HC are probably originated from a population of cells in the photoreceptor layer which are strongly coupled with the cones.

Adaptation, Ocular↗
PubMed1984

Responses of solitary retinal horizontal cells from Carassius auratus to L-glutamate and related amino acids.

Effects of L-glutamate and its analogues on membrane potentials of solitary horizontal cells were studied by intracellular recording. L-glutamate depolarized these cells at micromolar concentrations (greater than or equal to 10 microM), while D-glutamate and L-alpha-amino adipic acid produced slight depolarizations only at millimolar concentrations. Neither L- nor D-aspartate, even at millimolar doses, produced any change in solitary horizontal-cell resting potential. Solitary horizontal-cell responses to L-glutamate did not desensitize detectably. Responses to pairs of brief, ionophoretic pulses of L-glutamate were nearly equal in amplitude at inter-pulse intervals as short as 50 ms. Responses to maintained applications of low doses of L-glutamate did not decline for as long as 2 min. Depolarizing responses were produced by ionophoretic applications of L-glutamate near cell somata as well as dendrites. The mean sensitivity was 1.4 +/- 1.5 mV/nC with a maximum of 5.1 mV/nC. Depolarizing responses to L-glutamate reversed in polarity at membrane potentials between 0 and -20 mV, were accompanied by a decrease in membrane slope resistance, and were suppressed by replacement of extracellular sodium ions with choline. These results demonstrate that chemosensitivity of retinal horizontal cells to acidic amino acids persists after dissociation protocols, and in several respects resembles that found in horizontal cells in situ. These findings are consistent with the notion that retinal horizontal cells receive a synaptic input involving L-glutamate or a similar substance.

2-Aminoadipic Acid↗
PubMedDate not supplied

Simulation analysis of receptive-field size of retinal horizontal cells by ionic current model.

The size of the receptive field of retinal horizontal cells changes with the state of dark/light adaptation. We have used a mathematical model to determine how changes in the membrane conductance affect the receptive-field properties of horizontal cells. We first modeled the nonlinear membrane properties of horizontal cells based on ionic current mechanisms. The dissociated horizontal cell model reproduced the voltage-current (V-I) relationships for various extracellular glutamate concentrations measured in electrophysiological studies. Second, a network horizontal cell model was also described, and it reproduced the V-I relationship observed in vivo. The network model showed a bell-shaped relationship between the receptive-field size and constant glutamate concentration. The simulated results suggest that the calcium current is a candidate for the bell-shaped length constant relationship.

Animals↗
PubMed1990

Background-induced flicker enhancement in cat retinal horizontal cells. II. Spatial properties.

1. Intracellular recordings have been made from cat retinal horizontal cells stimulated with flickering test spots. Dim backgrounds increase flicker amplitudes in response to small but not large test stimuli. 2. This background-induced flicker enhancement has been measured for different slit- and square-test stimulus widths and the results compared with two spatial models for the enhancement effect. 3. In the "dark test-region" model it is argued that rods within the test region are unresponsive to background stimuli because of prior saturation by the test stimulus. Background-evoked rod signals decay passively from regions outside the test stimulus through a syncytial network into the recording site, where they act on the cone-to-horizontal-cell synapse, increasing its gain. 4. In the "changing length-constant" model rod signals reduce the length constant of a syncytial network by uncoupling the cells within it. This causes an increased response to small but not large test stimuli. 5. Both models are analytically evaluated with the use of a conductive-sheet approximation to the syncytial network. Expressions are derived for network polarization [(V(0, 0)] as a function of stimulus size. The specific stimulus shapes considered are disks, rectangles, slits, and squares in both bright and dark varieties. From these expressions predictions of response enhancement as a function of stimulus size are made for both models. 6. The dark test-region model provides for an exponential decay of flicker enhancement as a function of slit width but a steeper-than-exponential decay with the width of squares, in close agreement with experimental data. 7. The changing length-constant model makes qualitatively similar predictions. Flicker enhancement declines nearly exponentially with slit width. For square-shaped test stimuli the predicted decline of flicker enhancement with size is somewhat shallower than either the dark test-region-model curve or the experimentally determined curve. 8. As recorded in the same set of cells and under the same set of stimulus conditions (with the use of both slit- and square-test stimuli), the mean length constant of the peak-to-peak flicker component in the horizontal-cell response is 168 +/- 18 (SE) microns with the background and 232 +/- 45 microns in the dark. The mean length constant for the background-induced flicker enhancement, as fit by dark test-region-model curves, is 186 +/- 22 microns (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Hyperpolarization of fish retinal horizontal cells by kainate and quisqualate.

Kainic (KA) and quisqualic (QA) acids have a potent depolarizing action on a variety of neurones of the central nervous system, including retinal horizontal cells. We now report the novel finding that at low concentrations (1-3 microM), these 'excitatory' amino acids hyperpolarize horizontal cells of the fish retina. We show that the hyperpolarizing effects of both KA and QA are reversed by the gamma-aminobutyric acid (GABA) antagonist bicuculline, whereas a second GABA antagonist, picrotoxin, reverses the effects of KA, but not of QA. Neither GABA antagonist influences horizontal cell depolarization by 50 microM KA or 50 microM QA, thus the excitatory (depolarizing and inhibitory (hyperpolarizing) effects of the amino acids involve independent mechanisms. We provide evidence that the hyperpolarizing effects are not mediated by the dopaminergic pathways associated with retinal horizontal cells.

Animals↗