Ac. Koong et al., ACTIVATION OF POTASSIUM CHANNELS BY HYPOXIA AND REOXYGENATION IN THE HUMAN LUNG ADENOCARCINOMA CELL-LINE A549, Journal of cellular physiology, 156(2), 1993, pp. 341-347
Active oxygen species are generated in cells during pathophysiologic c
onditions such as inflammation and postischemic reperfusion. If oxygen
radical scavengers are added before reperfusion, then the magnitude o
f injury is reduced. We investigated whether free radicals generated f
ollowing exposure to hypoxia and reoxygenation activate voltage-depend
ent K+ ion channels in tumor cells in vitro. Using the technique of wh
ole cell voltage clamping, we recorded currents from two families of p
otassium (K+) channels that were activated following reoxygenation. On
e of these groups possessed the electrophysical characteristics of a t
etraethylammonium (TEA)-sensitive delayed rectifier channel and the ot
her possessed characteristics of a Tea-insensitive slow inactivating c
hannel. We present evidence which suggests that K+ channels are activa
ted following reoxygenation but not during the hypoxia phase. The K+ c
urrents decayed with time following reoxygenation. The decay character
istics of the K+ currents depended on the duration and level of hypoxi
a to which the cells were exposed. To determine whether activation of
K+ channels by reoxygenation was initiated by free radicals, we pretre
ated cells with N-Acetyl L-Cysteine (NAC), a free radical scavenger, a
nd found that this pretreatment abolished the currents induced by reox
ygenation. We also present evidence that free radicals do not directly
act on the channel itself, but activate a protein kinase which, in tu
rn, activates the K+ channels. Taken together, these results indicate
that one of the early responses to oxidative stress is the activation
of K+ currents. (C) 1993 Wiley-Liss, Inc.