Antagonistic properties of caged GABA compounds used for activation of GABAA receptors in neocortical pyramidal neurons

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http://urn.fi/URN:NBN:fi:hulib-201906283087
Title: Antagonistic properties of caged GABA compounds used for activation of GABAA receptors in neocortical pyramidal neurons
Author: Srinivasan, Rakenduvadhana
Contributor: University of Helsinki, Faculty of Biological and Environmental Sciences
Publisher: Helsingin yliopisto
Date: 2019
Language: eng
URI: http://urn.fi/URN:NBN:fi:hulib-201906283087
http://hdl.handle.net/10138/303615
Thesis level: master's thesis
Degree program: Neurotieteiden maisteriohjelma
Master's Programme in Neuroscience
Magisterprogrammet i neurovetenskap
Specialisation: Neurotiede
Neuroscience
Neurovetenskap
Abstract: Caged photolysable compounds have served to be pivotal to neuroscientific investigations; allowing the cognizing of molecular kinetics and properties of neuronal micro-machinery such as neurotransmitter receptors. Precision in terms of temporal and spatial resolution of neurotransmitter release endowed by photolysis has multitudinal applicabilities in the realm of GABAA receptors (GABAARs), their neuronal niche and effects on neuronal and network activity. Caged compounds, in their caged form, may display certain unideal traits such as undesired interactions with the system and antagonistic activity on the target receptor. This study aims to reevaluate the GABAAR antagonistic actions of caged Rubi-GABA, which was found to antagonize these receptors at significantly lower concentrations than those reported in the literature. Furthermore, this study electrophysiologically characterizes the possible antagonistic properties of a novel quinoline-derived UV-photolysable caged GABA compound, 8 DMAQ GABA, whose activity, in its caged form appears to have a much more favorable antagonism profile compared to the widely used RuBi-GABA. To assess the antagonistic effects of these compounds on GABAAR-mediated miniature inhibitory postsynaptic currents (mIPSCs) patch-clamp recordings were carried out in the whole-cell voltage clamp configuration on cortical layer 2/3 cortical pyramidal neurons in acute neocortical slices prepared from 16-18 day-old rat rats. The results of this study indicate a revised antagonism profile for caged Rubi-GABA, with marked GABAAR toxicity in the low micromolar range. The study also scrutinizes the photo-kinetic properties of both caged GABA compounds and reveals that the rate of GABA release from 8-DMAQ is slower than from RuBi-GABA.
Subject: Caged GABA
GABAA Receptors
Antagonism
Photo-activation
Neurotransmitter
Electrophysiology
RuBi-GABA
8-DMAQ GABA


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