Halothane decreases Na,K-ATPase, and Na channel activity in alveolar type II cells

Abstract

Background: Halothane alters surfactant biosynthesis and metabolism of alveolar type II cells. In addition to synthesizing surfactant, alveolar type II cells actively transport sodium (Na) from the alveolar space to the interstitium. Na enters the cells through amiloride-sensitive 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 transport activities. Methods: Epithelial type II cells from adult rat lungs 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 and 30 min. Na transport was then evaluated by direct measurement of radiolabeled ions uptake. In addition, the effects of halothane were assessed in the absence of extracellular calcium (Ca) with or without 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, an intracellular Ca chelating agent. Results: Exposure of epithelial type II cells to halothane reduced the activity of sodium, potassium-adenosine triphosphatase, and amiloride-sensitive Na channels, whereas Na cotransporters were unchanged. The decrease in sodium, potassium-adenosine triphosphatase activity was maximal for 30 rain of exposure and reached 50, 42, and 56% for halothane concentrations of 1, 2, and 4%, respectively, and did not change for longer exposure times. This effect was not prevented by either the absence of extracellular Ca or 1,2-bis(2-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid pretreatment. Exposure for 45 rain to 1% halothane also decreased Na channel activity by 46%. These effects were completely reversible after 30 min of recovery. Conclusions: Sodium, potassium-adenosine triphosphatase, and amiloride-sensitive Na channel activities are impaired by halothane in alveolar type II cells in vitro. This inhibition could reduce transepithelial Na transport.