Normal function of HERG K+ channels expressed in HEK293 cells requires basal protein kinase B activity.

The potential role of protein kinase B (PKB), a serine/threonine protein kinase, in regulating HERG (human ether-a-go-go related gene) K(+) channel function was investigated. Wortmannin (a phosphoinositide 3-kinase (PI3K) inhibitor) caused approximately 30% reduction of HERG current (I(HERG)) stably expressed in HEK293 cells. Transient transfection with the constitutively active PI3K in HERG-expressing HEK293 cells slightly increased ( approximately 7%) I(HERG) while a dominant negative PI3K significantly reduced I(HERG) ( approximately 25%) relative to results in vehicle-transfected cells. I(HERG) was approximately 35% greater in cells transfected with the constitutively activated PKB (caPKB), whereas it was approximately 47% smaller in cells transfected with dominant negative PKB (dnPKB). Basal activation of PKB was detected by immunocytochemistry. PKB activity was significantly enhanced in caPKB-transfected cells and nearly abolished in dnPKB-transfected cells. We conclude that normal HERG function in HEK293 cells requires basal activity of PKB. Our data represent the first evidence that PKB phosphorylation regulates K(+) channels.