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

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Abstract
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 ∼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 (∼7%) I HERG while a dominant negative PI3K significantly reduced I HERG (∼25%) relative to results in vehicle‐transfected cells. I HERG was ∼35% greater in cells transfected with the constitutively activated PKB (caPKB), whereas it was ∼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.