| During a synaptic transmission, the pre-synaptic neuron releases neurotransmitters into the synapse, where they bind to post-synaptic receptors specific to them, thereby propagating the signal. However, the non-specific adsorption of neurotransmitter molecules to lipid membranes has also been speculated to impact synaptic transmission. Though the clearance of adsorbed metabolic wastes has been suggested as an underlying vital function of sleep, a process conserved for all animals, the adsorption of neurotransmitters to lipid vesicles has rarely been quantitatively described. Thermodynamic measurements of adsorption for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) to model lipid membranes composed of 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DMPG) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) are presented for the first time in this study.;Lipids of varying lipid composition and concentration were prepared using an extruder. Isothermal titration calorimetry (ITC) was used alongside fitting models to derive thermodynamic parameters, including adsorption affinity, Kads. ITC results were obtained for the adsorption of GABA to 1:1 mixtures of DMPG and DMPC, with consistent fitted K ads values in the order of magnitude of 101 to 103 M--1. The size distribution of extruded lipids was characterized using dynamic light scattering (DLS), and ITC results were further supported with techniques such as concatenation and custom.;The system explored is physiologically significant. GABA is the most common inhibitory neurotransmitter, and neuronal membranes contain a high fraction (upwards of 20%) of anionic lipids. Consistent Kads values, obtained using ITC, for the affinity of neurotransmitters to receptor-free model lipids, suggests that adsorption is occurring as a non-specific interaction, shedding further insight towards the purpose of sleep. |
