Neurochemical Research

, Volume 18, Issue 4, pp 365–376 | Cite as

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

  • Eugene Roberts
  • Mark A. Sherman
Microanatomy and Metabolism


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.

Key Words

GABA electroneutrality information transmittal fidelity GABAergic function proton enhancement GABAA receptor cavity model 


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Copyright information

© Plenum Publishing Corporation 1993

Authors and Affiliations

  • Eugene Roberts
    • 1
  • Mark A. Sherman
    • 2
  1. 1.Department of NeurobiochemistryBeckman Research Institute of the City of HopeDuarte
  2. 2.Department of BiologyBeckman Research Institute of the City of HopeDuarte

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