The ionophore function of gamma-aminobutyric acid(A) (GABA(A)) receptors was studied by whole-cell patch clamp electrophysiology in primary cultures of rat cerebral cortex. Chloride ions were replaced for SCN(-) (thiocyanate) and HCO(-3) (bicarbonate) ions. The EC(50) values of the GABA(A) agonist muscimol (HCO(-3)>Cl(-)>SCN(-)) varied parallel with the free energies of dehydration of the anions, while the inhibition constants of the GABA(A) antagonist bicuculline methiodide were not affected. These findings might be relevant in the interpretation of the contribution of HCO(-3) versus Cl(-) currents to the pharmacological differences between depolarizing and hyperpolarizing GABA responses.
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