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1

Interaction between the serotoninergic and GABAergic systems in frog retina as revealed by electroretinogram

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Popova E., Kupenova P.
Acta Neurobiologiae Experimentalis
|
2017
|
tom 77
|
nr 4
Functional interactions between serotoninergic and GABAergic systems in the vertebrate retina are largely unknown. In this study, the effects of isolated or combined stimulation of the serotonin receptors (with 100 µM serotonin) and ionotropic GABAA and GABAC receptors (with 5 mM TACA) on the electroretinographic (ERG) ON (b‑wave) and OFF (d‑wave) responses were investigated in frog eyecup preparations. It was found that serotonin alone produced a significant enhancement of the b‑ and d‑wave amplitude, while TACA alone caused its marked diminution. The relative amplitude diminution, caused by the TACA treatment, was significantly smaller when TACA was applied on the background of the fully developed serotonin effect. This result suggests that the retinal serotoninergic system could diminish the effects of ionotropic GABA receptor activation on the ERG wave generator mechanisms. In order to separately evaluate the effects of the GABAC receptor activation, in a subset of experiments the effects of TACA or TACA + serotonin were tested during GABAA receptor blockade with 100 µM bicuculline. Bicuculline alone caused a marked increase of the b‑ and d‑wave amplitude. The stimulation of GABAC receptors (with TACA) during bicuculline action produced a strong diminution of the b‑ and d‑wave amplitudes. Similar relative decrease of the b‑wave amplitude was produced when TACA was applied in combination with serotonin, while the relative decrease of the d‑wave amplitude was less pronounced during treatment with serotonin + TACA than TACA alone. Our results demonstrate that there is an ON/OFF asymmetry in the receptors involved in the presumed interactions between serotoninergic and GABAergic systems. Serotonin may decrease the effects of GABAA receptor activation in the ON pathway, while it may decrease the effects of both GABAA and GABAC receptor activation in the OFF pathway.
2

Dopamine D2 receptor blockade differentially affects the light‑adapted turtle and frog electroretinogram

100%
Popova E., Kupenova P.
Acta Neurobiologiae Experimentalis
|
2018
|
tom 78
|
nr 4
The effects of dopamine D2‑class receptor blockade by sulpiride on the electroretinographic (ERG) b‑wave (ON response) and d‑wave (OFF response) were investigated in light‑adapted turtle (Trachemys scripta elegans) and frog (Rana ridibunda) eyecups. For turtle ERG, sulpiride (240 μM) produced an amplitude increase of the b‑ and d‑waves, while the 40 μM and 120 μM of sulpiride were ineffective. Alternatively, for frog ERG, a well‑developed and dose‑dependent b‑ and d‑wave amplitude decrease was obtained with 40 μM and 240 μM sulpiride. In both species, 240 μM sulpiride significantly affected the maximal voltage range of the ERG responses without altering their relative sensitivity (determined by the semi‑saturation point). The absolute sensitivity of the ON and OFF responses (evaluated by threshold estimation) was not significantly altered for turtle ERG, but it was decreased for frog ERG. The time characteristics of the ERG responses were unchanged in both species. Our results show important differences between dopamine D2‑class receptor‑mediated pathways in turtle and frog retina (revealed by ERG).
3

Effects of HCN channel blockade on the intensity‑response function of electroretinographic ON and OFF responses in dark adapted frogs

100%
Popova E., Kupenova P.
Acta Neurobiologiae Experimentalis
|
2020
|
tom 80
|
nr 2
Hyperpolarization‑activated and cyclic nucleotide‑gated (HCN) channels are well expressed in the vertebrate retina. Their role in formation of electroretinographic (ERG) responses to stimulus onset (b‑wave) and stimulus offset (d‑wave) are largely unknown. In this study we investigated the effects of pharmacological blockade of HCN channels (with ZD7288 or ivabradine) on the ERG b‑ and d‑waves in dark adapted frog eyecup preparations. Initially, the dose‑response relationship of ZD7288 effects on the b‑ and d‑waves was investigated. Afterwards, the effects of 75 μM ZD7288 on the stimulus ‑ response function of the ERG b‑ and d‑waves were explored over a wide intensity range (10 log units). Finally, the effects of 30 μM ivabradine on the same function were studied. Perfusion with 75 μM ZD7288 did not change the absolute and relative sensitivity of the ERG ON and OFF responses. It caused an enhancement of the d‑wave amplitude at all suprathreshold stimulus intensities, while the b‑wave amplitude was slightly enhanced only in the range of higher intensities. As a result of the greater blocker effect on the OFF response amplitude, the b/d amplitude ratio was significantly decreased over the whole intensity range. ZD7288 caused a prolongation of the b‑wave half‑width duration, but a shortening of the d‑wave half‑width duration at higher intensities. Similar results were obtained when 30 μM ivabradine was used for HCN channel blockade. Our results clearly demonstrate that the blockade of retinal HCN channels changes the balance between the ON and OFF responses in the distal frog retina. This ON/OFF imbalance may be one of the causes for visual disturbances reported in ivabradine treated patients.
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