Mechanism by which GABA, through its GABA(A) receptor, modulates glutamate release from rat cortical neurons in culture.
In cortical neurons, the GABA(A) agonist, muscimol, increases: (a) basal glutamate release (with a EC50 of 99 +/- 7 microM); (b) intracellular calcium and (c) membrane potential, all of these in a dose-dependent manner. These muscimol effects were specific since they were reversed by bicuculline, a GABA(A) antagonist. When the action of muscimol was measured at different KCl concentrations, an increase or decrease of the glutamate secretion was observed, depending on the KCl concentration in the medium. At low KCl concentration (5.6 mM of KCl), it depolarized, at 20 mM of KCl it had no effect, but at higher KCl concentrations (30-100 microM of KCl), it produced a hyperpolarization in these cells. The mechanism by which the GABA-Cl(-)-channel permits Cl- fluxes, inward or outward, depending on the membrane potential.
Herrero
M T
MT
Instituto de Bioquimica (Centro mixto CSIC-UCM) Facultad de Farmacia, Madrid, Spain.
Oset-Gasque
M J
MJ
López
E
E
Vicente
S
S
González
M P
MP
D000818:Animals; D001463:Barbiturates / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018118:Chloride Channels / Q000378:metabolism / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D018698:Glutamic Acid / Q000378:metabolism*; D017136:Ion Transport; D007555:Isoxazoles / Q000737:chemistry; D008564:Membrane Potentials; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D001463:Barbiturates; D018118:Chloride Channels; D002712:Chlorides; D005456:Fluorescent Dyes; D007555:Isoxazoles; D011963:Receptors, GABA-A; C052795:bis(1,3-dibutylbarbiturate)trimethine oxonol; D009118:Muscimol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D002118:Calcium