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American Journal of Respiratory Cell and Molecular Biology. Vol. 28, pp. 363-372, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.2002-0101OC

Large Conductance Ca2+-Activated K+ Channels Sense Acute Changes in Oxygen Tension in Alveolar Epithelial Cells

Sofija Jovanovic, Russell M. Crawford, Harri J. Ranki and Aleksandar Jovanovic

Tayside Institute of Child Health, Ninewells Hospital & Medical School, University of Dundee, Scotland, United Kingdom

Address correspondence to: Aleksandar Jovanovic, M.D., Ph.D., Tayside Institute of Child Health, Ninewells Hospital & Medical School, University of Dundee, Dundee, DD1 9SY Scotland, UK. E-mail: a.jovanovic{at}dundee.ac.uk

The rise in alveolar oxygen tension (PO2) that occurs as the newborn infant takes its first breaths induces removal of liquid from the lung lumen due to ion transport across the alveolar epithelium and the activity of alveolar Na+ channel (ENaC). In the present study, we have aimed to identify an ion conductance in alveolar epithelial A549 cells that responds to acute changes in PO2. Variation in PO2 did not affect single-channel ENaC activity. However, in these cells we have detected single-channel conductance having properties similar to those of large conductance Ca2+-activated K+ (BKCa) channels. Reverse transcriptase–polymerase chain reaction and Western blotting demonstrated presence of {alpha}-BKCa channel subunit and iberiotoxin, a blocker of BKCa channels, inhibited whole cell K+ current. Chronic changes in PO2 did not affect expression, recruitment, or function of BKCa channels in A549 cells. In contrast, acute changes of PO2 regulated the BKCa channel activity by controlling the channel mean open time. This effect of PO2 was insensitive to inhibitor of flavoproteins, diphenylene iodinium. In addition, decrease in PO2 and iberiotoxin induced membrane depolarization and Ca2+ oscillations in A549 cells. We conclude that BKCa channels serve as oxygen sensors in human alveolar A549 epithelial cells.

Abbreviations: large conductance Ca2+-activated K+, BKCa • alveolar Na+ channel, ENaC • alveolar oxygen tension, PO2 • reverse transcriptase–polymerase chain reaction, RT-PCR




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