6533b856fe1ef96bd12b1cd6
RESEARCH PRODUCT
The main determinant of furosemide inhibition on GABA(A) receptors is located close to the first transmembrane domain.
Sylvie JezequelRiikka MäkeläRaymonde KleinzEsa R. KorpiHartmut LüddensWulf HeversCarolin Jackelsubject
PharmacologyBase SequenceGABAA receptorVoltage clampProtein subunitXenopusAllosteric regulationCell MembraneMolecular Sequence DataXenopusBiologyIn Vitro Techniquesbiology.organism_classificationGABAA-rho receptorCell biologyGABA AntagonistsTransmembrane domainBiochemistryAllosteric RegulationFurosemideOocytesAnimalsGABA-A Receptor AntagonistsReceptordescription
Inhibitory GABA(A) receptors are regulated by numerous allosteric modulators, the most receptor-subtype specific of which is furosemide. It recognises receptors of the subunit composition alpha6beta2/3gamma2, restricted to cerebellar granule cells. To locate furosemide's site of action we constructed chimeras of the furosemide-sensitive alpha6 and the furosemide-insensitive alpha1 subunit, and expressed and studied them together with the beta3 and gamma2 subunits in Xenopus oocytes by the two-electrode voltage clamp technique. The inhibition of GABA-induced currents by furosemide mainly depended on a short domain proximal to the first transmembrane region of the alpha6 subunit.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1998-10-31 | European journal of pharmacology |