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GABA—The quintessential neurotransmitter: Electroneutrality, fidelity, specificity, and a model for the ligand binding site of GABAA receptors

  • Microanatomy and Metabolism
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Abstract

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.

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Authors and Affiliations

  1. Department of Neurobiochemistry, Beckman Research Institute of the City of Hope, 91010, Duarte, CA

    Eugene Roberts

  2. Department of Biology, Beckman Research Institute of the City of Hope, 91010, Duarte, CA

    Mark A. Sherman

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  1. Eugene Roberts
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Special issue dedicated to Dr. Claude Baxter.

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Roberts, E., Sherman, M.A. GABA—The quintessential neurotransmitter: Electroneutrality, fidelity, specificity, and a model for the ligand binding site of GABAA receptors. Neurochem Res 18, 365–376 (1993). https://doi.org/10.1007/BF00967239

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