Pflügers Archiv

, Volume 451, Issue 3, pp 474–478 | Cite as

Fenamates and diltiazem modulate lipid-sensitive mechano-gated 2P domain K+ channels

  • Masayuki Takahira
  • Mayumi Sakurai
  • Norimasa Sakurada
  • Kazuhisa Sugiyama
Ion Channels, Transporters


A swelling-activated, background K+ current in the corneal epithelium is characteristically activated by fenamates and inhibited by diltiazem. Fatty acids also stimulate this current, indicating that its origin is a lipid-sensitive mechano-gated 2P domain K+ channel. In the present study, modulation of TREK-1, TREK-2, and TRAAK channels by fenamates and diltiazem was examined. TREK-1, TREK-2, and TRAAK currents transiently expressed in COS-7 cells were recorded by the perforated-patch configuration. As previously reported, arachidonic acid (20 μM) stimulated all of these channels, and a volatile anesthetic, halothane (1 mM) augmented TREK-1 and TREK-2 but not TRAAK. Flufenamic acid (FA, 100 μM), niflumic acid (NA, 100 μM), and mefenamic acid (MA, 100 μM) markedly stimulated TREK-1, TREK-2, and TRAAK. The potency sequence for the activation of TREK-1 and TREK-2 was FA > NA = MA, and the potency sequence for the activation of TRAAK was FA = NA > MA. Diltiazem (1 mM) inhibited TREK-1 and TREK-2, but not TRAAK. In conclusion, fenamates are openers of the lipid-sensitive mechano-gated 2P domain K+ channels, and diltiazem may be a specific blocker for TREK. These novel findings could help to further understand channel functions of the mechano-gated 2P domain K+ channels.


Fenamates TREK TRAAK Diltiazem Potassium channels 2P domain Corneal epithelium 



The authors thank Bret A Hughes at University of Michigan and Hiroshi Sakurai for critical evaluation of the manuscript. This research was supported by Grant-in-Aid 11771043 and 13771018 for MT from the Ministry of Education, Japan.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Masayuki Takahira
    • 1
  • Mayumi Sakurai
    • 1
  • Norimasa Sakurada
    • 1
  • Kazuhisa Sugiyama
    • 1
  1. 1.Department of Visual Neuroscience & OphthalmologyKanazawa UniversityKanazawaJapan

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