PubMed 21953466

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ2 , Kv7.2

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

Authors: Xingjuan Chen, Xuan Zhang, Caixia Jia, Jiaxi Xu, Haixia Gao, Guohong Zhang, Xiaona Du, Hailin Zhang

Journal, date & volume: J. Biol. Chem., 2011 Nov 18 , 286, 39760-7

PubMed link:

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 βII 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 β. Furthermore, membrane depolarization enhanced PKC activity. The effects of both depolarization and PMA were blocked by a PKC inhibitor or PI4 kinase β RNA interference. Further results demonstrate that the depolarization selectively activated the PKC βII isoform and enhanced its interaction with PI4 kinase β. 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 β.