Activation of potassium channels by hypoxia and reoxygenation in the human lung adenocarcinoma cell line A549
- 1 August 1993
- journal article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 156 (2), 341-347
- https://doi.org/10.1002/jcp.1041560217
Abstract
Active oxygen species are generated in cells during pathophysiologic conditions such as illflammation and postischemic reperfusion. If oxygen radical scavengers are added before reperfusion, then the magnitude of injury is reduced. We inves‐tigated whether free radicals generated following exposure to hypoxia and reoxygenation activate voltage‐dependent K+ ion channels in tumor cells in vitro. Using the technique of whole cell voltage clamping, we recorded currents from two families of potassium (K+) channels that were activated following reoxygenation. One of these groups possessed the electrophysical characteristics of a tetraethylammonium (TEA)‐sensitive delayed rectifier channel and the other possessed characteristics of a Tea‐insensitive slow inactivating channel. We present evidence which suggests that K+ channels are activated following reoxygenation but not during the hypoxia phase. The K+ currents decayed with time following reoxygenation. The decay characteristics of the K+ currents depended on the duration and level of hypoxia to which the cells were exposed. To determine whether activation of K+ channels by reoxygenation was initiated by free radicals, we pretreated cells with N‐Acetyl L‐Cysteine (NAC), a free radical scavenger, and found that this pretreatment abolished the currents induced by reoxygenation. We also present evidence that free radicals do not directly act on the channel itself, but activate a protein kinase which, in turn, activates the K+ channels. Taken together, these results indicate that one of the early responses to oxidative stress is the activation of K+ currents.Keywords
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