HALOTHANE DECREASES NA,K-ATPASE, AND NA CHANNEL ACTIVITY IN ALVEOLAR TYPE-II CELLS

Background I-Halothane alters surfactant biosynthesis and metabolism o f alveolar type II cells. In addition to synthesizing surfactant, alve olar type II cells actively transport sodium (Na) from the alveolar sp ace to the interstitium. Na enters the cells through amiloride-sensiti ve Na channels or Na cotransporters and is extruded by a Na pump. The purpose of this study was to examine the effects of halothane on Na tr ansport activities. Methods: Epithelial type II cells from adult rat l ungs were exposed to halothane concentrations of 1, 2, and 4% from 0.5 -4 h. In some experiments, cells that were exposed to 1% halothane for 1 h were allowed to recover after replacement of the medium for 15 an d 30 min, Na transport was then evaluated by direct measurement of rad iolabeled ions uptake. In addition, the effects of halothane were asse ssed in the absence of extracellular calcium (Ca) with or without ,2-b is(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, an intracellular Ca chelating agent Results: Exposure of epithelial type II cells to ha lothane reduced the activity of sodium, potassium-adenosine triphospha tase, and amiloride-sensitive Na channels, whereas Na cotransporters w ere unchanged. The decrease in sodium, potassium-adenosine triphosphat ase activity was maximal for 30 min of exposure and reached 50, 42, an d 56% for halothane concentrations of 1, 2, and 4%, respectively, and did not change for longer exposure times. This effect was not prevente d by either the absence of extracellular-Ca or 1,2-bis(2- aminophenoxy )ethane-N,N,N' ,N'-tetraacetic acid pretreatment. Exposure for 45 min to 1% halothane also decreased Na channel activity by 46%. These effec ts were completely reversible after 30 min of recovery. Conclusions: S odium, potassium-adenosine triphosphatase, and amiloride-sensitive Na channel activities are impaired by halothane in alveolar type II cells ia vitro. This inhibition could reduce transepithelial Na transport.