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Hypoxia-induced inhibition of whole cell membrane currents and ion transport of A549 cells

¹Section III-Cardiology, ²Section VII-Sports Medicine, Department of Internal Medicine, and ³Department of Physiology and Pathophysiology, University of Heidelberg, 69115 Heidelberg, Germany

Submitted 25 November 2002 ; accepted in final form 29 December 2003

In excitable cells, hypoxia inhibits K channels, causes membrane depolarization, and initiates complex adaptive mechanisms. It is unclear whether K channels of alveolar epithelial cells reveal a similar response to hypoxia. A549 cells were exposed to hypoxia during whole cell patch-clamp measurements. Hypoxia reversibly inhibited a voltage-dependent outward current, consistent with a K current, because tetraethylamonium (TEA; 10 mM) abolished this effect; however, iberiotoxin (0.1 µM) does not. In normoxia, TEA and iberiotoxin inhibited whole cell current (–35%), whereas the K-channel inhibitors glibenclamide (1 µM), barium (1 mM), chromanol B293 (10 µM), and 4-aminopyridine (1 mM) were ineffective. ⁸⁶Rb uptake was measured to see whether K-channel modulation also affected transport activity. TEA, iberiotoxin, and 4-h hypoxia (1.5% O₂) inhibited total ⁸⁶Rb uptake by 40, 20, and 35%, respectively. Increased extracellular K also inhibited ⁸⁶Rb uptake in a dose-dependent way. The K-channel opener 1-ethyl-2-benzimidazolinone (1 mM) increased ⁸⁶Rb uptake by 120% in normoxic and hypoxic cells by activation of Na-K pumps (+60%) and Na-K-2Cl cotransport (+170%). However, hypoxic transport inhibition was also seen in the presence of 1-ethyl-2-benzimidazolinone, TEA, and iberiotoxin. These results indicate that hypoxia, membrane depolarization, and K-channel inhibition decrease whole cell membrane currents and transport activity. It appears, therefore, that a hypoxia-induced change in membrane conductance and membrane potential might be a link between hypoxia and alveolar ion transport inhibition.

whole cell patch clamp; calcium-activated potassium channels; sodium-potassium pump; sodium-potassium-chloride cotransport; membrane potential

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