GABA--the quintessential neurotransmitter: electroneutrality, fidelity, specificity, and a model for the ligand binding site of GABAA receptors.
Alone of the known neurotransmitters, GABA is an electroneutral zwitterion (pI = 7.3) at physiological pH. This confers the highest probability of successfully traversing densely packed synaptic gaps without interacting electrostatically with charged entities enroute, making GABA a high fidelity neurotransmitter. Inhibitory tone in the nervous system is coordinately coupled with physiological activity by means of the GABA system, acidification increasing GABA formation and its Cl- channel-opening efficacy, while decreasing its removal by transport and metabolic degradation. The above, together with diminution upon acidification of the postsynaptic efficacy of glutamate on excitatory NMDA receptors constitutes a sensitively responsive mechanism by which protons control levels of neural activity, locally and globally. A model made of the GABA binding site of GABAA receptors based on H-bond and hydrophobic interactions makes it seem unlikely that any other substance known to occur in nerve tissue would give rise to a high noise level at GABAA receptors.
Department of Neurobiochemistry, Beckman Research Institute of the City of Hope, Duarte, CA 91010.
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Sherman
D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D004563:Electrochemistry; D008958:Models, Molecular; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid