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Fenamates Stimulate BKCa Channel Activity in the Human Osteoblast-Like MG-63 Cells
  1. Sheng-Nan Wu,
  2. Chung-Ren Jan,
  3. Hung-Ting Chiang
  1. 1From the Department of Medical Education and Research (S.-N.W., C.-R.J.) Kaohsiung-Veterans General Hospital, Kaohsiung City, Taiwan, ROC
  2. 2Department of Internal Medicine (H.-T.C.), Kaohsiung-Veterans General Hospital, Kaohsiung City, Taiwan, ROC.
  1. Address correspondence to: Sheng-Nan Wu, MD, PhD, Department of Medical Education and Research, Kaohsiung-Veterans General Hospital, No 386, Ta-Chung 1st Road, Kaohsiung City, Taiwan, ROC. E-mail snwu{at}
  2. Supported by grants from the National Science Council (NSC-89-2320-B-075B-016) and Kaohsiung-Veterans General Hospital (VGHKS90-06, VGHKS90-73, and VTY89-P3-23), Taiwan, ROC.


Background The fenamates, a family of nonsteroidal anti-inflammatory drugs that are derivatives of N-phenylanthranilic acid, are the inhibitors of cyclo-oxygenase. The ionic mechanism of actions of these compounds in osteoblasts is not well understood.

Methods The effects of the fenamates on ionic currents were investigated in a human osteoblast-like cell line (MG-63) with the aid of the whole-cell and inside-out configurations of the patch-clamp technique.

Results In MG-63 cells, niflumic acid and meclofenamic acid increased K+ outward currents (I K). The niflumic acid-stimulated I K was reversed by subsequent application of iberiotoxin or paxilline, yet not by that of glibenclamide or apamin. In the inside-out configuration, niflumic acid (30 μmol/L) added to the bath did not modify single-channel conductance but increased the activity of large-conductance Ca2+-activated K+ (BKCa) channels. The EC50 values for niflumic acid- and meclofenamic acid-induced channel activity were 22 and 24 μmol/L, respectively. Niflumic acid (30 μmol/L) and meclofenamic acid (30 μmol/L) shifted the activation curve of BKCa channels to less positive membrane potentials. Membrane stretch potentiated niflumic acid-stimulated channel activity. The rank order of potency for the activation of BKCa channels in these cells was niflumic acid = meclofenamic acid > tolfenamic acid > flufenamic acid > nimesulide. Evans blue and nordihydroguaiaretic acid increased channel activity; however, indomethacin, piroxicam, and NS-398 had no effect on it.

Conclusions The fenamates can stimulate BKCa channel activity in a manner that seems to be independent of the action of these drugs on the prostaglandin pathway. The activation of the BKCa channel may hyperpolarize the osteoblast, thereby modulating osteoblastic function.

  • fenamates
  • nonsteroidal anti-inflammatory drugs
  • Ca2+-activated K+ current
  • large-conductance Ca2+-activated K+ channels
  • osteoblasts

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