Membrane depolarization increases membrane PtdIns(4,5)P2 levels through mechanisms involving PKC ?II and PI4 kinase.

ABSTRACT: In a previous study, we showed that membrane depolarization induced elevation of membrane phosphatidylinositol 4,5-bisphosphates (PtdIns(4,5)P(2), also known as PIP(2)) and subsequently increased the KCNQ2/Q3 currents expressed in Xenopus oocytes through increased PI4 kinase activity. In this study, the underlying mechanism for this depolarization-induced enhancement of PIP(2) synthesis was further investigated. Our results indicate that activation of protein kinase C (PKC) isozyme ?II was responsible for the enhanced PIP(2) synthesis. We found that phorbol-12-myristate, 13-acetate (PMA), an activator of PKC, mimicked the effects of the membrane depolarization by increasing KCNQ2/Q3 activity, elevating membrane PIP(2) levels and increasing activity of PI4 kinase ?. Furthermore, membrane depolarization enhanced PKC activity. The effects of both depolarization and PMA were blocked by a PKC inhibitor or PI4 kinase ? RNA interference. Further results demonstrate that the depolarization selectively activated the PKC ?II isoform and enhanced its interaction with PI4 kinase ?. These results reveal that the depolarization-induced elevation of membrane PIP(2) is through activation of PKC and the subsequent increased activity of PI4 kinase ?.

SUBMITTER: Chen X 

PROVIDER: S-EPMC3220586 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature