Postsynaptic Response Kinetics Are Controlled by a Glutamate Transporter at Cone Photoreceptors

1998 ◽  
Vol 79 (1) ◽  
pp. 190-196 ◽  
Author(s):  
Lubor Gaal ◽  
Botond Roska ◽  
Serge A. Picaud ◽  
Samuel M. Wu ◽  
Robert Marc ◽  
...  
Keyword(s):  
Voltage Dependence ◽  
Light Flash ◽  
Horizontal Cell ◽  
Glutamate Transporter ◽  
Light Response ◽  
Horizontal Cells ◽  
Cone Photoreceptors ◽  
Postsynaptic Response ◽  
Glutamate Concentration ◽  
Voltage Dependent

Gaal, Lubor, Botond Roska, Serge A. Picaud, Samuel M. Wu, Robert Marc, and Frank S. Werblin. Postsynaptic response kinetics are controlled by a glutamate transporter at cone photoreceptors. J. Neurophysiol. 79: 190–196, 1998. We evaluated the role of the sodium/glutamate transporter at the synaptic terminals of cone photoreceptors in controlling postsynaptic response kinetics. The strategy was to measure the changes in horizontal cell response rate induced by blocking transporter uptake in cones with dihydrokainate (DHK). DHK was chosen as the uptake blocker because, as we show through autoradiographic uptake measurements, DHK specifically blocked uptake in cones without affecting uptake in Mueller cells. Horizontal cells depolarized from about −70 to −20 mV as the exogenous glutamate concentration was increased from ∼1 to 40 μM, so horizontal cells can serve as “glutamate electrodes” during the light response. DHK slowed the rate of hyperpolarization of the horizontal cells in a dose-dependent way, but didn't affect the kinetics of the cone responses. At 300 μM DHK, the rate of the horizontal cell hyperpolarization was slowed to only 17 ± 8.5% (mean ± SD) of control. Translating this to changes in glutamate concentration using the slice dose response curve as calibration in Fig. 2 , DHK reduced the rate of removal of glutamate from ∼0.12 to 0.031 μM/s. The voltage dependence of uptake rate in the transporter alone was capable of modulating glutamate concentration: we blocked vesicular released glutamate with bathed 20 mM Mg2+ and then added 30 μM glutamate to the bath to reestablish a physiological glutamate concentration level at the synapse and thereby depolarize the horizontal cells. Under these conditions, a light flash elicited a 17-mV hyperpolarization in the horizontal cells. When we substituted kainate, which is not transported, for glutamate, horizontal cells were depolarized but light did not elicit any response, indicating that the transporter alone was responsible for the removal of glutamate under these conditions. This suggests that the transporter was both voltage dependent and robust enough to modulate glutamate concentration. The transporter must be at least as effective as diffusion in removing glutamate from the synapse because there is only a very small light response once the transporter is blocked. The transporter, via its voltage dependence on cone membrane potential, appears to contribute significantly to the control of postsynaptic response kinetics.[Figure: see text]

Voltage-Dependent Uptake Is a Major Determinant of Glutamate Concentration at the Cone Synapse: An Analytical Study

1998 ◽  
Vol 80 (4) ◽  
pp. 1951-1960 ◽  
Author(s):  
Botond Roska ◽  
Lubor Gaal ◽  
Frank S. Werblin
Keyword(s):  
Analytical Study ◽  
Glutamate Uptake ◽  
Glutamate Transporter ◽  
Light Response ◽  
Synaptic Cleft ◽  
Major Determinant ◽  
Glutamate Concentration ◽  
Voltage Dependent ◽  
Interdependent Relationships ◽  
Close Fit

Roska, Botond, Lubor Gaal, and Frank S. Werblin. Voltage-dependent uptake is a major determinant of glutamate concentration at the cone synapse: an analytical study. J. Neurophysiol. 80: 1951–1960, 1998. It was suggested that glutamate concentration at the synaptic terminal of the cones was controlled primarily by a voltage-dependent glutamate transporter and that diffusion played a less important role. The conclusion was based on the observation that the rate of glutamate concentration during the hyperpolarizing light response was dramatically slowed when the transporter was blocked with dihydrokainate although diffusion remained intact. To test the validity of this notion we constructed a model in which the balance among uptake, diffusion, and release determined the flow of glutamate into and out of the synaptic cleft. The control of glutamate concentration was assumed here to be determined by two relationships; 1) glutamate concentration is the integral over the synaptic volume of the rates of release, uptake, and diffusion, and 2) membrane potential is the integral over the membrane capacitance of the dark, leak, and transporter-gated chloride current. These relationships are interdependent because glutamate uptake via the transporter is voltage dependent and because the transporter-gated current is concentration dependent. The voltage and concentration dependence of release and uptake, as well as the light-elicited, transporter-gated, and leak currents were measured in other studies. All of these measurements were incorporated into our predictive model of glutamate uptake. Our results show a good quantitative fit between the predicted and the measured magnitudes and rates of change of glutamate concentration, derived from the two interdependent relationships. This close fit supports the validity of these two relationships as descriptors of the mechanisms underlying the control of glutamate concentration, it verifies the accuracy of the experimental data from which the functions used in these relationships were derived, and it lends further support to the notion that glutamate concentration is controlled primarily by uptake at the transporter.

Dual effect of glycine on horizontal cells of the tiger salamander retina

1991 ◽  
Vol 66 (6) ◽  
pp. 1993-2001 ◽  
Author(s):  
S. Borges ◽  
M. Wilson
Keyword(s):  
Opposite Effect ◽  
Horizontal Cell ◽  
Light Response ◽  
Membrane Resistance ◽  
Horizontal Cells ◽  
Field Size ◽  
Dual Effect ◽  
Light Responses ◽  
Low Concentrations ◽  
High Concentrations

1. The effects of glycine on horizontal cells have been examined by microelectrode recording from superfused retinas isolated from the salamander. 2. Low concentrations of glycine (less than 50 microM) hyperpolarized horizontal cells and increased the magnitude of their light responses. Millimolar concentrations produced the opposite effect of depolarizing these cells and reducing their light response amplitudes. 3. In the presence of Co2+ and Mg2+ at concentrations sufficient to suppress the light response, millimolar glycine still exerted a depolarizing effect on horizontal cells, implying that this effect was largely a direct one on horizontal cell membranes. 4. Although both the rod and the cone contributions to horizontal cell light responses were reduced by millimolar glycine, rod input was reduced more, suggesting that millimolar glycine may also exert a presynaptic effect. 5. Strychnine (10 microns) antagonized the effects of millimolar glycine and, in the absence of exogenously applied glycine, caused horizontal cells to hyperpolarize and their light responses to increase in amplitude. This result implies that, in darkness, glycine is tonically released onto horizontal cells and maintains them in a state of partial depolarization. 6. The low-concentration effect of glycine was accompanied by an increased membrane resistance and receptive field size but no change in the balance of rod and cone input. 7. Low concentrations of glycine were often seen to cause a speeding of light responses, whereas high concentrations sometimes caused a slowing of response kinetics. Response kinetics were found to correlate with horizontal cell dark membrane potential so that, positive to -30 mV, depolarization slowed responses whereas kinetics at more negative values were largely independent of voltage.

Bifurcation analysis of nonlinear retinal horizontal cell models. II. Network properties

1990 ◽  
Vol 64 (1) ◽  
pp. 248-261 ◽  
Author(s):  
R. L. Winslow ◽  
S. Ma
Keyword(s):  
Horizontal Cell ◽  
Membrane Currents ◽  
Horizontal Cells ◽  
Synaptic Conductance ◽  
Cell Models ◽  
Voltage Dependent ◽  
Full Complement ◽  
Network Properties ◽  
Light Stimuli ◽  
Coupling Conductance

1. We have previously presented a model of horizontal-cell soma isolated from fish retina. The model consists of a synaptic conductance representing input from photoreceptors in parallel with voltage-dependent membrane currents. Membrane-current models are based on I-V curves measured in isolated fish horizontal cells. Bifurcation theory was used to analyze model properties. The major findings of this study were 1) the inward Ca2+ current must be inactivated to account for horizontal-cell resting potentials and hyperpolarizing responses to light stimuli in a background of dark, and 2) the synaptic conductance controls the bifurcation structure of the model, with bistable behavior occurring at small and monostable behavior occurring at larger values of the synaptic conductance. The synaptic conductance at the point of transition from bistable to monostable behavior corresponds to the activation of as few as 100 synaptic channels. Thus tonic synaptic input from photoreceptors and inactivation of the inward Ca2+ current act to “linearize” responses of isolated horizontal-cell models. 2. The model described in this paper extends these analyses to large networks of horizontal cells in which each cell is coupled resistively to its nearest neighbors and is modeled with the use of the full complement of nonlinear membrane currents. Network responses to arbitrary patterns of conductance change (simulating inputs from photoreceptors), current-, or voltage-clamp stimuli are computed using the Newton iteration. The Newton descent direction is computed using either conjugate gradient (CG) or preconditioned CG algorithms. 3. An analysis of network stability properties is performed. Network I-V curves are computed by voltage-clamping the center node and computing the current required to maintain the clamp voltage. Computations are performed on networks of model cells in which the Ca2+ current is fully activated and the synaptic conductance is zero, thus making each cell as nonlinear as possible. Coupling conductance values slightly greater than 100 pS provide a current shunt sufficient to prevent the generation of Ca2+ action potentials in the network. This coupling conductance corresponds to the conductance of as few as two gap-junction channels and is more than two orders of magnitude less than the coupling known to exist between pairs of cultured horizontal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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

1999 ◽  
Vol 16 (5) ◽  
pp. 811-818 ◽  
Author(s):  
CHENGBIAO LU ◽  
DAO-QI ZHANG ◽  
DOUGLAS G. McMAHON
Keyword(s):  
Single Channel ◽  
Lucifer Yellow ◽  
Horizontal Cell ◽  
Electrical Coupling ◽  
Cell Voltage ◽  
Horizontal Cells ◽  
Simultaneous Application ◽  
Dependent Inactivation ◽  
Cellular Junctions ◽  
Voltage Dependent

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 μM, −9% reduction in coupling) and dopamine (100–300 μM, −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.

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

1993 ◽  
Vol 102 (2) ◽  
pp. 277-294 ◽  
Author(s):  
C Pfeiffer-Linn ◽  
E M Lasater
Keyword(s):  
Cyclic Amp ◽  
Calcium Channels ◽  
Calcium Current ◽  
Horizontal Cell ◽  
Calcium Currents ◽  
Horizontal Cells ◽  
White Bass ◽  
Cell Calcium ◽  
Cone Type ◽  
Voltage Dependent

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.

scholarly journals Local signals in mouse horizontal cell dendrites

2017 ◽  
Author(s):  
Camille A. Chapot ◽  
Christian Behrens ◽  
Luke E. Rogerson ◽  
Tom Baden ◽  
Sinziana Pop ◽  
...  
Keyword(s):  
Glutamate Release ◽  
Horizontal Cell ◽  
Horizontal Cells ◽  
Single Type ◽  
Mouse Retina ◽  
Gabaergic Interneuron ◽  
List Type ◽  
Cone Photoreceptor ◽  
Cone Photoreceptors ◽  
Temporal Properties

SummaryThe mouse retina contains a single type of horizontal cell, a GABAergic interneuron that samples from all cone photoreceptors within reach and modulates their glutamatergic output via parallel feedback mechanisms. Because horizontal cells form an electrically-coupled network, they have been implicated in global signal processing, such as large scale contrast enhancement. Recently, it has been proposed that horizontal cells can also act locally at the level of individual cone photoreceptors. To test this possibility physiologically, we used two-photon microscopy to record light stimulus-evoked Ca2+signals in cone axon terminals and horizontal cell dendrites as well as glutamate release in the outer plexiform layer. By selectively stimulating the two mouse cone opsins with green and UV light, we assessed whether signals from individual cones remain “isolated” within horizontal cell dendritic tips, or whether they spread across the dendritic arbour. Consistent with the mouse‘s opsin expression gradient, we found that the Ca2+signals recorded from dendrites of dorsal horizontal cells were dominated by M- and those of ventral horizontal cells by S-opsin activation. The signals measured in neighbouring horizontal cell dendritic tips varied markedly in their chromatic preference, arguing against global processing. Rather, our experimental data and results from biophysically realistic modelling support the idea that horizontal cells can process cone input locally, extending the “classical” view of horizontal cells function. Pharmacologically removing horizontal cells from the circuitry reduced the sensitivity of the cone signal to low frequencies, suggesting that local horizontal cell feedback shapes the temporal properties of cone output.HighlightsLight-evoked Ca2+signals in horizontal cell dendrites reflect opsin gradientChromatic preferences in neighbouring dendritic tips vary markedlyMouse horizontal cells process cone photoreceptor input locallyLocal horizontal cell feedback shapes the temporal properties of cone outputeTOC BlurbChapot et al. show that local light responses in mouse horizontal cell dendrites inherit properties, including chromatic preference, from the presynaptic cone photoreceptor, suggesting that their dendrites can provide “private” feedback to cones, for instance, to shape the temporal filtering properties of the cone synapse.

Voltage-dependent ionic currents in solitary horizontal cells isolated from cat retina

1992 ◽  
Vol 68 (4) ◽  
pp. 1143-1150 ◽  
Author(s):  
Y. Ueda ◽  
A. Kaneko ◽  
M. Kaneda
Keyword(s):  
Potassium Current ◽  
Horizontal Cell ◽  
Potassium Currents ◽  
Ionic Currents ◽  
Horizontal Cells ◽  
Membrane Properties ◽  
Resting Potential ◽  
Delayed Rectifier ◽  
Cat Retina ◽  
Voltage Dependent

1. Horizontal cells of the cat retina were isolated by enzymatic dissociation. Two types of horizontal cells were identified: the axonless (A-type) horizontal cell having four to six thick, long (approximately 100 microns) dendrites, and the short-axon (B-type) horizontal cell having many (> 5) fine, short (approximately 30 microns) dendrites. 2. Membrane properties of isolated horizontal cells were analyzed under current-clamp and voltage-clamp conditions. In the A-type cell, the average resting potential was -55 mV and the mean membrane capacitance was 110 pF, whereas values in the B-type cell were -58 mV and 40 pF, respectively. The A-type cell showed long-lasting Ca spikes, but B-type cells had no Ca spikes. 3. Five types of voltage-dependent ionic currents were recorded: a sodium current (INa), a calcium current (ICa), and three types of potassium currents. Potassium currents consisted of potassium current through the inward rectifier (Ianomal), transient outward potassium current (IA), and potassium current through the delayed rectifier (IK(v)). INa was recorded only from A-type cells. Other currents were recorded from both types of cells. 4. INa activated when cells were depolarized from a holding potential (Vh) of -95 mV, and it was maximal at -25 mV. This current was blocked by tetrodotoxin. Approximately half of the A-type cells had INa, but no B-type cell had this current. 5. L-type ICa, an inward-going sustained current, was activated with depolarization more positive than -25 mV. Current amplitude reached a maximal value near 15 mV and became smaller with further depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristics and ionic processes involved in feedback spikes of turtle cones

1980 ◽  
Vol 206 (1165) ◽  
pp. 439-463 ◽  
Keyword(s):  
Horizontal Cell ◽  
Light Response ◽  
Membrane Resistance ◽  
Feedback Mechanism ◽  
Horizontal Cells ◽  
Critical Threshold ◽  
Feedback Effects ◽  
Pharmacological Agents ◽  
Bright Flash ◽  
Resistance Decrease

In about 20% of the cones of untreated retinas of turtles, bright flash illumination of the periphery of their receptive field evokes a spike through the feedback mechanism from the L-horizontal cell. Such feed­back spikes, never observed with central stimulation, are labile, butafter they have disappeared they can be regained by depolarizing the cone. Feedback spikes are actual regenerative responses, since they show a critical threshold potential, are facilitated by cone depolarization and are blocked by hyperpolarization. They are associated with a membrane resistance decrease; tetrodotoxin (10 -5 M) does not block them. High Ca 2+ media facilitate their appearance, but their effect is transient because of the cone hyperpolarization and the light response block that Ca 2+ ions induce. Sr 2 + ions (4-10mM) facilitate the discharge of feedback spikes in response to peripheral illumination in every cone, whether or not it has previously shown feedback effects. In Sr 2+ media, feedback spikes are stable and can be evoked by dim lights. Ba 2+ (2-6 mM) also facilitates and stabilizes the discharge of feedback spikes. Co 2+ and D-600 block the feedback spikes. Pharmacological agents that depolarize the L-horizontal cells, such as GABA, glutamate or nicotine, also block the feedback spikes. Both Sr 2+ and Ba 2+ also induce the appearance of spontaneous and off spikes, which are also blocked by Co 2+ , but these are not related to the feedback mechanism. These results strongly suggest that every turtle cone receives a feedback input from the L-horizontal cells, which would be able to induce an increase of the cone Ca 2+ con­ductance, which may become regenerative.

Effects of calcium on rod and cone inputs to horizontal cells of the tiger salamander retina

1994 ◽  
Vol 11 (2) ◽  
pp. 363-368 ◽  
Author(s):  
Xiong-Li Yang ◽  
Samuel M. Wu
Keyword(s):  
Signal Transmission ◽  
Horizontal Cell ◽  
Light Response ◽  
Horizontal Cells ◽  
Cone Voltage ◽  
Tiger Salamander ◽  
Peak Voltage ◽  
Selective Suppression ◽  
Isolated Retina ◽  
Synaptic Gain

AbstractEffects of extracellular calcium on signal transmission between photoreceptors and horizontal cells (HCs) are studied in superfused isolated retina of the larval tiger salamander. Horizontal cell light response is optimal when extracellular Ca2+ is maintained between 1–2 mM. Ca2+ levels beyond this range in either direction significantly reduce the HC light response amplitude. When extracellular Ca2+ is lowered from 2 mM to 0.5 mM, the rod input to HCs is reduced whereas the cone input is not affected. In comparison, the peak voltage responses of rods are not changed whereas the cone voltage responses are enhanced in 0.5 mM Ca2+. The selective suppression of rod input to HCs is probably due to the interplay of three factors: (1) the photocurrents, (2) voltage- and time-dependent membrane currents in photoreceptors, and (3) the Ca2-dependent synaptic gain between photoreceptors and HCs.

Potassium currents in the inner segment of single retinal cone photoreceptors

1990 ◽  
Vol 64 (6) ◽  
pp. 1929-1940 ◽  
Author(s):  
A. V. Maricq ◽  
J. I. Korenbrot
Keyword(s):  
Voltage Dependence ◽  
Delayed Rectifier ◽  
Half Maximum ◽  
Cone Photoreceptors ◽  
Delayed Rectifier Current ◽  
Maximum Activation ◽  
Voltage Dependent ◽  
Kinetics Of ◽  
K Currents ◽  
Steepness Factor

1. The K+ currents of cone inner segments isolated from the retina of a lizard were studied with the use of tight-seal electrodes in the whole cell configuration. To conduct these studies other identified currents in the cell were blocked. Co2+ blocked a voltage-dependent Ca2+ current and a Ca2(+)-dependent Cl- current, and Cs+ blocked an inward-rectifying current partially carried by K+. 2. The cells sustained a voltage-dependent K+ current that was blocked by tetraethylammonium (TEA)+ and had characteristics typical of the delayed rectifier. However, we found no evidence for the existence of “A”-type K+ currents or Ca2(+)-dependent K+ currents. 3. The delayed-rectifier current was nearly ideally selective for K+. Increasing external K+ concentration 10-fold shifted the reversal potential by 55 mV. 4. Analysis of the voltage dependence of the activation of the delayed-rectifier current revealed the existence of two distinct subclasses of this current. We referred to them as IdrL and IdrH for low and high threshold of voltage activation. 5. IdrL activated at voltages above -70 mV. Its dependence on voltage was described by Boltzmann's function with average half-maximum activation at -51 mV and steepness factor k = 7.5 mV. IdrH activated at voltages above -50 mV. Its dependence on voltage was described by Boltzmann's function with average half-maximum activation at -4.6 mV and steepness factor k = 17.1 mV. 6. Of nine cells analyzed in detail, one demonstrated IdrH alone, whereas the remaining had a variable mixture of the two current subtypes. At maximum activation the current through IdrL ranged between 0.3 and 0.5 of the total delayed-rectifier current. 7. The kinetics of activation of the total delayed-rectifier current were described by the sum of two exponentials the amplitudes and time constants of which were voltage dependent. However, the kinetics of the current subtypes were not resolved individually. The current inactivated slowly with a single-exponential time course that was voltage dependent. 8. The voltage dependence of the delayed-rectifier current indicates the current is active in a cone photoreceptor in the dark. The current is 20-30 pA in amplitude at the dark-membrane potential and outwardly directed. 9. IdrL may generate a rapid relaxation of photovoltages activated by dim lights--those that hyperpolarize the membrane by only a few millivolts. The delayed-rectifier currents help shape the action potentials that can be generated in isolated cone photoreceptors

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