Abstract

The GABA molecule is the major inhibitory neurotransmitter in the mammalian central nervous system. Through binding to post-synaptic neurons, GABA reduces the neuronal excitability by hyperpolarization. Correct binding between the GABA molecules and its receptors relies on molecular recognition. Earlier studies suggest that recognition is determined by the geometries of the molecule and its receptor. We employed dielectric relaxation spectroscopy (DRS) to study the conformation and dielectric properties of the GABA molecule under physiologically relevant laboratory conditions. The dielectric properties of GABA investigated have given us new insights about the GABA molecule, such as how they interact with each other and with water molecules at different temperatures (22°C and 37.5°C). Higher temperature leads to lower viscosity, thus lower relaxation time. The change in the GABA relaxation time due to concentration change is more associated with the solution viscosity than with the GABA dipole moment. A resonance behavior was observed with high GABA concentrations at physiological temperature, where there might be a phase transition at a certain temperature for a given GABA concentration that leads to a sudden change of the dielectric properties.

Highlights

  • The GABA molecule is the major inhibitory neurotransmitter in the mammalian central nervous system

  • Two sets of parameters were extracted; the contribution of the GABA molecules to the total dielectric behavior of the solution, and the contribution of the water molecules. ǫ∞ is a joint parameter for both GABA and water molecules and indicates the high frequency limit of the permittivity

  • We hypothesize that there is a phase transition in the GABA molecules, which might indicate a significant change in GABA properties at the physiological temperature

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Summary

Introduction

The GABA molecule is the major inhibitory neurotransmitter in the mammalian central nervous system. GABA mediates its inhibitory effect by hyperpolarizing the membrane and by shutting down the excitatory ­inputs[2]. This prevents the neurons from reaching the threshold of an action potential, hindering the release of neurotransmitters. Ottosson et al.[7] investigated the conformation of the GABA molecule in liquid water They found that GABA adopts a nearly linear, unfolded conformation in aqueous solution at room temperature, which rises the question: How will the GABA conformation change when we increase the temperature? Shitaka et al.[4] investigated the dielectric features of GABA for molecular recognition by receptors.

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