Bicarbonate and thiocyanate ions affect the gating of gamma-aminobutyric acid(A) receptors in cultured rat cortical cells.
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.
Maksay
G
G
Chemical Research Center of the Hungarian Academy of Sciences, Department of Molecular Pharmacology, P.O. Box 17, H-1525 Budapest, Hungary. maksay@chemres.hu
Fodor
L
L
Bielik
N
N
Tarnawa
I
I
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010599:Pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013861:Thiocyanates / Q000378:metabolism*
D001639:Bicarbonates; D018118:Chloride Channels; D018755:GABA Agonists; D018756:GABA Antagonists; D007476:Ionophores; D011963:Receptors, GABA-A; D013861:Thiocyanates; D009118:Muscimol; C017069:bicuculline methiodide; D001640:Bicuculline