title: Acute and chronic effects of eicosapentaenoic acid on voltage-gated sodium channel expressed in cultured human bronchial smooth muscle cells.
abstract: This study investigated acute and chronic effects of eicosapentaenoic acid (EPA) on voltage-gated Na+ current (I(Na)) expressed in cultured human bronchial smooth muscle cells (hBSMCs). The whole-cell voltage clamp technique and quantitative real-time RT-PCR analysis were applied. The alterations in the fatty acid composition of phospholipids after treatment with EPA were also examined. Extracellular application of EPA produced a rapid and concentration-dependent suppression of tetrodotoxin-sensitive I(Na) with the half-maximal inhibitory concentration of 2 microM. After washing out EPA with albumin, I(Na) returned to the control level. Similar inhibitory effects were observed regarding other fatty acids (docosahexaenoic, arachidonic, stearic, and oleic acids), but EPA was the most potent inhibitor. The effect of EPA on I(Na) was not blocked by nordihydroguaiaretic acid and indometacin, and was accompanied by a significant shift of the steady-state inactivation curve to more negative potentials. In cells chronically treated with EPA, the EPA content of the cell lipid fraction (mol%) increased time-dependently, while arachidonic acid (AA) decreased, resulting in an increase of EPA to AA ratio. Then, the level of mRNA (SCN9A) encoding I(Na) decreased significantly. These results provide novel evidence that EPA not only rapidly inhibits I(Na), but also reduces the mRNA levels of the Na+ channel after cellular incorporation of EPA in cultured hBSMCs.
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Jo
authors.forename: Haruko
authors.initials: H
authors.lastname: Iida
authors.forename: Shinya
authors.initials: S
authors.lastname: Kishida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Imuta
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Oonuma
authors.forename: Taiji
authors.initials: T
authors.lastname: Nagata
authors.forename: Hajime
authors.initials: H
authors.lastname: Hara
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Iwasawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Soma
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sato
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D015640:Ion Channel Gating; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D015222:Sodium Channels; D015118:Eicosapentaenoic Acid