ACTIVATION OF POTASSIUM CHANNELS CONTRIBUTES TO HYPOXIC INJURY IN PROXIMAL TUBULES

Authors
Citation
Wb. Reeves et Sv. Shah, ACTIVATION OF POTASSIUM CHANNELS CONTRIBUTES TO HYPOXIC INJURY IN PROXIMAL TUBULES, The Journal of clinical investigation, 94(6), 1994, pp. 2289-2294
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
0021-9738
Volume
94
Issue
6
Year of publication
1994
Pages
2289 - 2294
Database
ISI
SICI code
0021-9738(1994)94:6<2289:AOPCCT>2.0.ZU;2-4
Abstract
The mechanisms responsible for the loss of cell potassium during renal ischemia are poorly understood. The present studies examined the hypo thesis that potassium channels are activated as an early response to h ypoxia and contribute to potassium loss independent from an inhibition of active K+ uptake. Potassium flux in suspensions of freshly isolate d rat proximal tubules was measured using an ion-selective electrode. Exposure of the tubules to hypoxia for only 2.5 min resulted in a rise in the passive leak rate of K+ but no decrease in active K+ uptake. T he passive leak of K+ was associated with a 40% decrease in cell ATP c ontent. The passive K+ efflux was inhibited by 5 mM Ba2+ (95%) and by 15 mM tetraethylammonium (85%) suggesting that K+ channels were the pr imary route of K+ movement. The effects of K+ channel blockade on the development of hypoxic injury were also examined. Tetraethylammonium a nd glibenclamide, an inhibitor of ATP-sensitive K+ channels, reduced h ypoxic injury as assessed by the release of lactate dehydrogenase or m easurement of DNA damage. These results suggest that activation of Kchannels is an early response to hypoxia and contributes to hypoxic re nal injury.