Hypoxia-induced inhibition of whole cell membrane currents and ion transport of A549 cells.
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 microM) does not. In normoxia, TEA and iberiotoxin inhibited whole cell current (-35%), whereas the K-channel inhibitors glibenclamide (1 microM), barium (1 mM), chromanol B293 (10 microM), and 4-aminopyridine (1 mM) were ineffective. (86)Rb uptake was measured to see whether K-channel modulation also affected transport activity. TEA, iberiotoxin, and 4-h hypoxia (1.5% O(2)) inhibited total (86)Rb uptake by 40, 20, and 35%, respectively. Increased extracellular K also inhibited (86)Rb uptake in a dose-dependent way. The K-channel opener 1-ethyl-2-benzimidazolinone (1 mM) increased (86)Rb 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.
Karle
Christoph
C
Section III-Cardiology, Department of Internal Medicine, Medical Clinic and Policlinic, University of Heidelberg, Germany.
Gehrig
Tobias
T
Wodopia
Ralf
R
Höschele
Sabine
S
Kreye
Volker A W
VA
Katus
Hugo A
HA
Bärtsch
Peter
P
Mairbäurl
Heimo
H
D045744:Cell Line, Tumor; D002712:Chlorides / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008175:Lung Neoplasms; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000378:metabolism; D012414:Rubidium Radioisotopes; D012964:Sodium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology
D002712:Chlorides; D010455:Peptides; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D012414:Rubidium Radioisotopes; D028021:Sodium-Potassium-Chloride Symporters; D019789:Tetraethylammonium; C064719:iberiotoxin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium