title: Membrane depolarization increases membrane PtdIns(4,5)P2 levels through mechanisms involving PKC βII 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 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.
authors.affiliation: Key Laboratory of Neural and Vascular Biology, Ministry of Education, Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei, 050017, China.
authors.forename: Xingjuan
authors.initials: X
authors.lastname: Chen
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Caixia
authors.initials: C
authors.lastname: Jia
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Xu
authors.forename: Haixia
authors.initials: H
authors.lastname: Gao
authors.forename: Guohong
authors.initials: G
authors.lastname: Zhang
authors.forename: Xiaona
authors.initials: X
authors.lastname: Du
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D006801:Humans; D051658:KCNQ2 Potassium Channel / Q000235:genetics / Q000378:metabolism; D051659:KCNQ3 Potassium Channel / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D015778:Minor Histocompatibility Antigens; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000235:genetics / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta; D034622:RNA Interference; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D002273:Carcinogens; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; C496915:Kcnq2 protein, rat; C496918:Kcnq3 protein, rat; D015778:Minor Histocompatibility Antigens; D019269:Phosphatidylinositol 4,5-Diphosphate; D029867:Xenopus Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D013755:Tetradecanoylphorbol Acetate