Dual action of isoflurane on the γ-aminobutyric acid (GABA)-mediated currents through recombinant α1β2γ(2L)-GABA(A)-receptor channels

Susanne Neumahr, Gerhard Hapfelmeier, Michaela Scheller, Hajo Schneck, Christian Franke, Eberhard Kochs

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

22 Zitate (Scopus)

Abstract

Isoflurane (ISO) increased the agonist-induced chloride flux through the γ-aminobutyric acid A receptor (GABA(A)R). This may reflect an anesthetic- induced increase in the apparent agonist affinity. A dual effect of anesthetics was postulated for both the nicotinic acetylcholine receptor (nAChR) and the GABA(A)R. We tested the hypothesis that, in addition to a blocking effect, ISO increases γ-aminobutyric acid (GABA)-gated currents through recombinant GABA(A)R channels. HEK293 cells were transfected with rat cDNA for α12,γ(2L) subunits. Currents elicited by 1 mM or 0.01 mM GABA, respectively, alone, or with increasing concentrations of ISO, were recorded by using standard patch clamp techniques. ISO reduced the peak current elicited by 1 mM GABA. Currents induced by 0.01 mM GABA were potentiated by small ISO (twofold at 0.5 mM ISO) and inhibited by larger concentrations. Withdrawal of ISO and GABA induced rebound currents, suggesting an open-channel block by ISO. These currents increased with increasing concentrations of ISO. At large concentrations of ISO, the inhibitory effect predominated and was caused by, at least partly, an open- channel block. At small concentrations of ISO, potentiation of the GABA-gated currents was more prominent. This dual action of ISO indicates different binding sites at the GABA(A)R. The balance between potentiation and block depends on the concentrations of both ISO and GABA.

OriginalspracheEnglisch
Seiten (von - bis)1184-1190
Seitenumfang7
FachzeitschriftAnesthesia and Analgesia
Jahrgang90
Ausgabenummer5
DOIs
PublikationsstatusVeröffentlicht - 2000
Extern publiziertJa

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