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A Akopian

Publications and source records attributed to A Akopian.

51 records · Page 3Linked to original sources
PubMed1996

D2 dopamine receptor-mediated inhibition of a hyperpolarization-activated current in rod photoreceptors.

1. Using the whole cell patch clamp method, we investigated the effect of dopamine on a hyperpolarization-activated current (Ih) in the inner segments of rod photoreceptors of the Xenopus retina. 2. Ih was elicited by hyperpolarizing voltage steps to -120 mV from a holding potential of -40 mV. Dopamine reversibly reduced Ih in a dose-dependent manner. Dopamine-mediated inhibition of Ih was blocked by the D2 dopamine antagonist sulpiride. 3. The D2 dopamine agonist quinpirole (0.1-20 microM) inhibited Ih whereas the D1 agonist SKF-38393 (100 microM) had no effect on Ih. Quinpirole-induced inhibition of Ih was blocked by sulpiride, but not by the D4 antagonist, clozapine. The D3 agonists (+/-)-7-hydroxy-2-dipropylaminotetralin hydrochloride and trans-7-hydroxy-2[N-propyl-N-(3'-iodo-2'-propenyl)amino]-tetralin maleate were, respectively, 5 and 100 times less effective than quinpirole in inhibiting Ih. 4. Quinpirole failed to reduce Ih when the internal solution contained GDP beta S (500 microM). Internal application GTP gamma S (300 microM) progressively and irreversibly reduced Ih and blocked a further reduction by quinpirole, indicating that the inhibition of Ih by quinpirole involves a G protein. 5. The inhibition of Ih by quinpirole was not affected by intracellularly applied adenosine 3',5'-cyclic monophosphate (cAMP) or by the protein kinase inhibitor H-7, indicating that a cAMP-mediated second messenger cascade does not participate in the dopamine-mediated inhibition. 6. Ih was not altered when the patch pipette contained a nominally Ca(2+)-free internal solution, but the inhibition of Ih by quinpirole was abolished, suggesting an involvement of Ca(2+) in the quinpirole-induced effect. 7. We conclude that a D2 dopamine receptor modulates Ih through the activation of a G protein and that intracellular Ca2+, but not cAMP, plays a key role in this process. 8. The reduction of Ih by dopamine may reduce the ability of rods to signal time-modulated light stimuli.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Feedback from luminosity horizontal cells mediates depolarizing responses of chromaticity horizontal cells in the Xenopus retina.

It has been proposed that the depolarizing responses of chromaticity horizontal cells (C-HCs) to red light depend on a feedback signal from luminosity horizontal cells (L-HCs) to short-wavelength-sensitive cones in the retinas of lower vertebrates. In this regard we studied the C-HCs of the Xenopus retina. C-HCs and L-HCs were identified by physiological criteria and then injected with neurobiotin. The retina then was incubated with peanut agglutinin, which stains red-but not blue-sensitive cones. Electron microscopic examination revealed that L-HCs contact all cone classes, whereas C-HCs contact only blue-sensitive cones. Simultaneous recordings from C-HC/L-HC pairs established that when the L-HC was saturated by a steady bright red light, C-HCs alone responded to a superimposed blue stimulus. In response to red test flashes, the C-HC response was delayed by approximately 30 msec with respect to the L-HC response. Isolated HCs of both subtypes were examined by whole-cell patch clamp. Both responded to kainate with sustained inward currents and to quisqualate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) with desensitizing currents from a negative holding potential; i.e., both have AMPA-type glutamate receptors. gamma-Aminobutyric acid or glycine opened a chloride channel in the L-HC, whereas the C-HC was unresponsive to either inhibitory amino acid. Since glycine has been shown to abolish selectively the depolarizing response of the C-HC, this finding and other pharmacological data strongly implicate the L-HC in the underlying circuit. Moreover, because the C-HC does not respond to gamma-aminobutyric acid, the neurotransmitter of the L-HC, by elimination, a feedback synapse from L-HC to blue cone is the most plausible mechanism for the creation of depolarizing responses in C-HCs.

Animals↗
PubMed1994

From dialysis to basic paediatric nephrology: an unorthodox project applied in Yerevan, Armenia.

Following the earthquake in December 1988, a long-term project was developed: starting from haemodialysis, it was extended to basic nephrology and urology, with a programme for schooling and psychosocial care. Medical training had first priority. The programme relied on robust and often second-hand equipment and voluntary work. The approach chosen (an inverse help programme, from sophisticated to basic medicine) strongly stimulated motivation and proved to be practicable.

Adolescent↗
PubMed1994

Modulation of transient outward potassium current by GTP, calcium, and glutamate in horizontal cells of the Xenopus retina.

1. Membrane currents of luminosity horizontal cells (L-HCs) and chromatic horizontal cells (C-HCs) isolated from the Xenopus retina were characterized using the whole-cell patch-clamp technique. 2. The current-voltage curve for the L-HC had a characteristic negative slope conductance in the voltage range of -30 to -10 mV that was not evident in the C-HC. 3. A transient outward 4-aminopyridine-sensitive potassium current (A-current) was the most prominent current in C-HCs but was also present in L-HCs. A-current characteristics in the two horizontal cell (HC) classes were closely similar. Its threshold of activation was above -45 mV. The half-voltage of inactivation was close to -70 mV. The decay of the A-current was fit by a single exponential with time constants of 30 and 40 ms at depolarizing voltage steps to -10 and +30 mV, respectively. 4. The voltage for 50% A-current inactivation shifted toward negative potentials shortly after we established the whole-cell configuration. This shift was changed to more positive potentials by internal application of guanosine 5'-triphosphate, resulting in a significant overlap of A-current activation and inactivation functions near -40 mV, which is well within the normal operating range of the HC. 5. Internal application of the G-protein activator GTP gamma S shifted the voltage-dependent inactivation of the A-current toward positive potentials by +15 mV. In contrast, GDP beta S shifted the inactivation curve by about -10 mV, similar to what was observed in untreated cells. 6. GTP and GTP gamma S increased the rate of recovery from inactivation and slowed down the rate of inactivation of the A-current enabled by a depolarizing prepulse. 7. Glutamate superfused in the bath solution significantly accelerated the rate of inactivation of A-current induced by depolarizing prepulses. The rate of A-current recovery from inactivation, however, was not affected by glutamate. 8. Removal of calcium from the bath solution reversibly decreased the amplitude of the A-current without a significant shift in its threshold of activation.

Animals↗
PubMed1994

The effects of L-glutamate, AMPA, quisqualate, and kainate on retinal horizontal cells depend on adaptational state: implications for rod-cone interactions.

We studied the responses of isolated and intact luminosity-type horizontal cells (L-HC) in the Xenopus retina to L-glutamate (L-glu) and its analogs. Isolated L-HCs studied with whole-cell patch clamp responded to L-glu, kainate (KA), AMPA, or quisqualate (quis) with inward currents from a holding potential of -60 mV, associated with a conductance increase. The current elicited by KA was relatively large and sustained, whereas AMPA or quis evoked a desensitizing current. Coapplication of quis and KA resulted in a smaller current and conductance change than that evoked by a pulse of either alone at the same concentration. This finding suggests that the L-HC has a single subtype of glutamate receptor that responds to both quis and KA. Prior exposure to dopamine enhanced the KA-evoked current about twofold. In the superfused eyecup we found that L-HC responses to quinoxalinediones (CNQX or DNQX) and to L-glu, KA, AMPA, and quis varied as a function of adaptational state. When driven exclusively by either cones or by rods, CNQX/DNQX hyperpolarized the L-HC and reduced its light response, without altering response kinetics, indicating that both rods and cones communicate with L-HCs at ionotropic glutamatergic synapses. Under mesopic conditions, however, as CNQX or DNQX reduced cone input, the rod input to the L-HC increased up to fivefold in magnitude and had slowed kinetics. The depolarizing response of the L-HC to L-glu, AMPA, or quis was relatively small and transient under photopic conditions, but was much larger and sustained when the eyecup was dark adapted. The D1 dopamine antagonist SCH 23390 potentiated the response to quis. In contrast, responses to KA were largest in light-adapted eyecups, were potentiated by a D1 dopamine agonist, SKF 38393, and were reduced by SCH 23390. We hypothesize that the segregated populations of glutamate receptors in the L-HC opposite cone and rod synaptic endings can be separately modulated to respond differentially to the native transmitter, glutamate. In photopic and mesopic states the dominant cone input tonically inhibits rod to L-HC communication. This inhibition appears to occur at the postsynaptic membrane and may be mediated by second messengers.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Effects of background illuminations on the receptive field size of horizontal cells in the turtle retina are mediated by dopamine.

Intracellular recordings from luminosity-type horizontal cells of the turtle retina were used to analyze the effects of steady and flickering background illumination on the size of their receptive fields. Both types of background illumination reduce the size of the receptive field to about the same extent. The reduction seems largely due an increase in the coupling resistance between horizontal cells. The effects of both types of background illumination are sensitive to the dopamine antagonist fluphenazine. This suggests that steady and flickering illuminations stimulate the release of endogenous dopamine.

Animals↗
PubMed1991

Short-term potentiation of off-responses in turtle horizontal cells.

Depolarizing responses to light off were studied in turtle horizontal cells using intracellular recording in the everted eyecup preparation. In many cells the off-response showed two components (fast and slow) which could overshoot beyond the steady-state dark level. The peak amplitudes of the fast and slow components increased with increasing duration of the light stimulus. A similar enhancement of the off-responses could also be produced by repetitive stimulation with brief flashes. However, the degree of enhancement produced by repetitive stimulation was greater than could be produced by increasing stimulus duration, and the latency of the onset of depolarization was longer, suggesting that the enhancement produced by repetitive stimulation involves an additional mechanism. Dramatic enhancement of the off-response by stimuli which did not affect the on-response during light indicates that the off-response may contain information not present in the on-response. The fast component of the off-response was suppressed to a greater degree than other components by reducing extracellular calcium or in the presence of 500 microM cobalt, suggesting that this component may involve a calcium current.

Animals↗
PubMedDate not supplied

Activation of metabotropic glutamate receptors decreases a high-threshold calcium current in spiking neurons of the Xenopus retina.

Two types of spiking neuron were identified among acutely dissociated neurons from the Xenopus retina by their responses to a depolarizing current step: single spikers and multiple spikers. In culture, multiple spikers had perikaryal diameters > 15 microns, whereas single spikers had smaller somata, 5-10 microns in diameter. Using a conventional whole-cell patch-clamp technique, both T- and L-type calcium currents were identified in multiply spiking cells whereas only an L-type current was present in singly spiking cells. The metabotropic glutamate receptor (mGluR) agonist trans-(1S-3R)-1-amino-1,3-cyclopentane-dicarboxylic acid (trans-ACPD) significantly decreased the L-type calcium current by 46 +/- 3% (mean +/- S.E.M.) in both types of cell but had only a minor effect on the T-type current in multiply spiking neurons. In the presence of 50 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 100 microM quisqualate (a potent mGluR1/5 agonist) decreased the L-type calcium current by 47 +/- 9% but had no effect on the T-type current. The selective mGluR4/6/7 agonist (+/-) 2-amino-4-phosphonobutyric acid (L-AP4, 100 microM), and the mGluR2/3 agonist (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine (L-CCG1, 100 microM) decreased the L-type calcium current by 12 +/- 3% and 14 +/- 2%, respectively. The inhibition of calcium current by trans-ACPD was reduced when the patch pipette contained the G-protein inhibitor, GDP beta S. The presence of the G-protein activator GTP gamma S in the patch pipette irreversibly reduced the L-type calcium current, but was without effect on the T-type current. Heparin applied intracellularly significantly reduced the inhibitory effect of quisqualate, indicating an involvement of the inositol triphosphate (IP3) pathway in the mGluR-induced reduction of calcium current. Replacement of internal EGTA with BAPTA significantly reduced the inhibitory effect of quisqualate. In contrast, internal application of cAMP did not prevent an inhibition of calcium current by quisqualate. Thus, the mechanism by which calcium current is inhibited by mGluR seems not to involve an intracellular cAMP cascade. Our findings indicate that activation of mGluR1/5 results in the inhibition of a high-threshold calcium current. This process is mediated by the activation of a G-protein and is consistent with inhibition occurring by an IP3-stimulated release of internal calcium.

Action Potentials↗