Received for publication December 5, 2005.
Revised January 6, 2006.
Accepted for publication January 6, 2006.

Halothane Modifies Directly Na⁺ and K⁺ Channel Activities in Cultured Human Alveolar Epithelial Cells

Abstract

During inhalational anesthesia halogenated gases are in direct contact with the alveolar epithelium, where they may affect transepithelial ion and fluid transport. The effects of halogenated gases in vivo on epithelial Na⁺ and K⁺ channels, which participate in alveolar liquid clearance, remain unclear. In the present study the effects of halothane (1, 2 and 4% atm) on ion channel function in cultured human alveolar cells were investigated using the patch-clamp technique. After exposure to 4% halothane, amiloride-sensitive whole-cell inward currents increased by 84±22% while tetraethylammonium-sensitive outward currents decreased by 63±7%. These effects, which occurred within 30 seconds, remained for 30-minute periods of exposure to the gas, were concentration-dependent and reversible upon wash-out. Pre-treatment with amiloride prevented 90±7% of the increase in inward currents without change in outward currents, consistent with an activation of amiloride-sensitive epithelial sodium channels. Tetraethylammonium obliterated 90±9 % of the effect of halothane on outward currents, without change in inward currents, indicating inhibition of Ca⁺⁺-activated K⁺ channels. These channels were identified in excised patches to be small conductance Ca⁺⁺-activated K⁺ channels. These effects of halothane were not modified after inhibition of cytosolic phospholipase A2 by aristolochic acid. Exposure of the cells to either trypsin or to low Na⁺ completely prevented the increase in amiloride-sensitive currents induced by halothane, suggesting a release of Na+ channels self inhibition. Thus halothane modifies differentially and independently Na⁺ and K⁺ permeabilities in human alveolar cells.

Key words: Ion channel regulation, Single channel kinetics

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