Temperature Dependence of the Microwave Dielectric Properties of γ‑Aminobutyric Acid

Jie Hou, Sisay Mebre Abie, Runar Strand-Amundsen, Yuri M. Galperin, Joakim Bergli, Christin Schuelke, Sina Hashemizadeh, and Ørjan Grøttem Martinsen, Scientific Reports 2021, Volume 11, Article Number 18082, online 10 September 2021; doi: 10.1038/s41598-021-97178-7

γ‑Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system. Through binding to post-synaptic neurons, GABA reduces neuronal excitability by hyperpolarization. Correct binding between the GABA molecules and its receptors relies on molecular recognition. Findings from 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 GABA, such as how the GABA molecules interact with each other and with water molecules at different temperatures (22°C and 37.5°C). Higher temperatures tend lower the viscosity, thus lowering relaxation times. The change in the GABA relaxation time due to concentration change is more associated with the solution viscosity than with the GABA dipole moment. 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 an abrupt change in dielectric properties.

The scientific and technical impact of the study can be summarized as:

  • The GABA molecule was studied for the first time over a physiologically relevant temperature range (22 – 37.5°C)
  • Dielectric spectroscopy, performed with advanced implementation of open-ended coaxial probe technology, demonstrated significant behavioral changes in the complex permittivity of the GABA molecule in solution at high concentration and physiological temperature, possibly caused by a phase transition in the GABA molecule
  • Dielectric spectroscopy was also used to study the conformation of GABA, showing that, as physiological temperature is approached, the molecule exhibits a more folded topology with decreasing relaxation times, which might affect molecular recognition mechanisms and lead to incorrect binding of GABA to receptors
  • Clinical findings on GABA conformation in patients can facilitate investigations of whether the condition of the patient is due to incorrect GABA binding to receptors or to a deficiency in GABA levels,  knowledge that could be used to develop new strategies to combat brain diseases associated with altered GABA signaling