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GENERAL ARTICLES

Halothane Stimulates a Na+H+ Antiporter Involved in the Regulation of Intracellular pH in Alveolar Epithelial Cells

Philippe Juvin, MD^*, Christine Clerici, MD, PhD, Alain Loiseau, PhD, Jean Mantz, MD, PhD^*, Michel Aubier, MD, Gérard Friedlander, MD, PhD, and Jean-Marie Desmonts, MD^*

*Departement d’Anesthésie, Hôpital Bichat-Claude Bernard, Paris; Laboratoire de Physiologie, Hôpital Avicenne, Bobigny; and Faculté de Médecine Bichat, Paris, France

Address correspondence and reprint requests to Philippe Juvin, MD, Departement d’Anesthésie, Hôpital Bichat-Claude Bernard. 46, Rue Henri Huchard, 75877 Paris Cedex 18, France. Address e-mail to philippe.juvin{at}bch.ap-hop-paris.fr

Changes in intracellular pH (pHi) of alveolar type II (ATII) cells have been involved in the pathophysiology of pulmonary edema. ATII cells have evolved several ions transporters to regulate their pHi, including a Na⁺H⁺ antiporter. Because halothane alters the activity of ion transporters in various cells types, it may also affect the activity of this Na⁺H⁺ antiporter. This study was performed 1) to characterize a Na⁺H⁺ antiporter in a model of ATII cells and 2) to investigate the effect of halothane on the activity of this antiporter. ATII cells were obtained from primary rat ATII cells transfected with a mutant of simian virus SV40 large T antigen (SV40-T2), and their pHi was monitored using the pH-sensitive fluorescent probe 2'-7' (bis carboxyethyl)-5(6')-carboxyfluorescein. We demonstrated in vitro that 1) a Na⁺H⁺ antiporter (apparent Km 6.8 ± 3.4 mM, Vmax 0.0105 ± 0.0013 UpHi/s) regulates the pHi of SV40-T2 cells and 2) at clinically relevant concentrations (10^-3 to 10^-5 M) and for a short exposure duration (60 min), halothane enhances the activity of this antiporter. Because ATII cell acidification has been associated with alterations in the alveolar epithelial barrier, halothane-induced intracellular alkalinization might exhibit some protective effect in clinical situations, such as aspiration pneumonia.

Implications: In vitro, halothane induces an intracellular alkalinization of pneumocytes II via the activation of a Na⁺H⁺ antiporter. Because acidification of these cells has been associated with alterations in the alveolar epithelial barrier, halothane might exhibit some protective effect in clinical situations, such as aspiration pneumonia.

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