Acute and chronic effects of eicosapentaenoic acid on voltage-gated sodium channel expressed in cultured human bronchial smooth muscle cells.
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.
Jo
Taisuke
T
Department of Cardiovascular and Respiratory Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Iida
Haruko
H
Kishida
Shinya
S
Imuta
Hiroyuki
H
Oonuma
Hitoshi
H
Nagata
Taiji
T
Hara
Hajime
H
Iwasawa
Kuniaki
K
Soma
Masaaki
M
Sato
Yoshiaki
Y
Nagase
Takahide
T
Nagai
Ryozo
R
Nakajima
Toshiaki
T
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
D012333:RNA, Messenger; D015222:Sodium Channels; D015118:Eicosapentaenoic Acid