BACKGROUND: Volatile anesthetics act primarily through upregulating the activity of γ-aminobutyric acid type A (GABA_A) receptors. They also exhibit antiinflammatory actions in the lung. Rodent alveolar type II (ATII) epithelial cells express GABA_A receptors and the inflammatory factor cyclooxygenase-2 (COX-2). The goal of this study was to determine whether human ATII cells also express GABA_A receptors and whether volatile anesthetics upregulate GABA_A receptor activity, thereby reducing the expression of COX-2 in ATII cells.

METHODS: The expression of GABA_A receptor subunits and COX-2 in ATII cells of human lung tissue and in the human ATII cell line A549 was studied with immunostaining and immunoblot analyses. Patch clamp recordings were used to study the functional and pharmacological properties of GABA_A receptors in cultured A549 cells.

RESULTS: ATII cells in human lungs and cultured A549 cells expressed GABA_A receptor subunits and COX-2. GABA induced currents in A549 cells, with half-maximal effective concentration of 2.5 µM. Isoflurane (0.1-250 µM) enhanced the GABA currents, which were partially inhibited by bicuculline. Treating A549 cells with muscimol or with isoflurane (250 µM) reduced the expression of COX-2, an effect that was attenuated by cotreatment with bicuculline.

CONCLUSIONS: GABA_A receptors expressed by human ATII cells differ pharmacologically from those in neurons, exhibiting a higher affinity for GABA and lower sensitivity to bicuculline. Clinically relevant concentrations of isoflurane increased the activity of GABA_A receptors and reduced the expression of COX-2 in ATII cells. These findings reveal a novel mechanism that could contribute to the antiinflammatory effect of isoflurane in the human lung.

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