GABAA responses in hippocampal neurons are potentiated by glutamate.
In the mammalian cortex, glutamate and gamma-aminobutyric acid (GABA) are the principal transmitters mediating excitatory and inhibitory synaptic events. Glutamate activates cation conductances that lead to membrane depolarization whereas GABA controls chloride conductances that produce hyperpolarization. Here we report that the GABAA-activated conductance in hippocampal pyramidal cells is enhanced by glutamate at concentrations below that required for its excitatory action. The GABA-potentiating effect can be induced, with comparable potency, by several glutamate analogues such as quisqualate, N-methyl-D-aspartate (NMDA), kainate and, surprisingly, by D-2-amino-5-phosphonovalerate (APV), an antagonist for NMDA receptors. Data from dose-response curves show that glutamate enhances the GABAA conductance without significantly changing GABA binding affinity. The low concentration of glutamate needed to enhance GABAA responses raises the possibility that glutamate modulates the strength of GABA-mediated transmission in the cortex.
Stelzer
A
A
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Wong
R K
RK
D000818:Animals; D004357:Drug Synergism; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D005971:Glutamates; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid