Ligand-gated ion channel proteins in the postsynaptic membrane selectively transmit cationic (e.g., acetylcholine) or anionic neurotransmitters (e.g., GABA) into the postsynaptic cleft between neurons, where they bind to their specific receptors, eliciting excitatory or inhibitory effects on action potentials. The response of these receptors to their agonists has often complex time courses, but the mechanisms that lead to these time courses are unknown. The membrane associations of GABA and acetylcholine were quantified with SPR to test the hypothesis that neurotransmitters affect receptor activity indirectly, by membrane association and alteration of membrane properties, which in turn might modulate receptor activity. The two neurotransmitters differ in their membrane affinity. Whereas GABA associates with the membrane with a dissociation constant, Kd ~ 1.5 �M, acetylcholine shows a dissociation constant in the mM range. At saturation, both neurotransmitters reach a neurotransmitter to lipid ratio of approximately 1:4.

Association of the neurotransmitters GABA and acetylcholine with lipid bilayer membranes

245th National Meeting (2013)

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