Action of the Photochrome Glyght on GABAergic Synaptic Transmission in Mouse Brain Slices

Petukhova, Elena and Ponomareva, Daria and Rustler, Karin and Koenig, Burkhard and Bregestovski, Piotr (2022) Action of the Photochrome Glyght on GABAergic Synaptic Transmission in Mouse Brain Slices. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23 (18): 10553. ISSN , 1422-0067

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Abstract

Glyght is a new photochromic compound described as an effective modulator of glycine receptors at heterologous expression, in brain slices and in zebrafish larvae. Glyght also caused weak inhibition of GABA(A)-mediated currents in a cell line expressing alpha 1/beta 2/gamma 2 GABA(A) receptors. However, the effects of Glyght on GABAergic transmission in the brain have not been analysed, which does not allow a sufficiently comprehensive assessment of the effects of the compound on the nervous system. Therefore, in this study using whole-cell patch-clamp recording, we analysed the Glyght (100 mu M) action on evoked GABAergic inhibitory postsynaptic currents (eIPSCs) in mice hippocampal slices. Two populations of cells were found: the first responded by reducing the GABAergic eIPSCs' amplitude, whereas the second showed no sensitivity to the compound. Glyght did not affect the ionic currents' amplitude induced by GABA application, suggesting the absence of action on postsynaptic GABA receptors. Additionally, Glyght had no impact on the paired-pulse modulation of GABAergic eIPSCs, indicating that Glyght does not modulate the neurotransmitter release mechanisms. In the presence of strychnine, an antagonist of glycine receptors, the Glyght effect on GABAergic synaptic transmission was absent. Our results suggest that Glyght can modulate GABAergic synaptic transmission via action on extrasynaptic glycine receptors.

Item Type: Article
Uncontrolled Keywords: GLYCINERGIC INHIBITION; ION CHANNELS; RECEPTORS; LIGHT; PLASTICITY; EXPRESSION; NEURONS; Glyght; photopharmacology; azobenzene; glycine receptors; GABA(A) receptors
Subjects: 500 Science > 540 Chemistry & allied sciences
Divisions: Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König
Depositing User: Dr. Gernot Deinzer
Date Deposited: 02 Feb 2024 07:13
Last Modified: 02 Feb 2024 07:13
URI: https://pred.uni-regensburg.de/id/eprint/58263

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