Niflumic and Flufenamic Acids Are Potent Reversible Blockers of Ca2(+)-activated Cl- Channels in Xenopus Oocytes

The effects of niflumic acid and flufenamic acid, two nonsteroidal anti-inflammatory agents known to block anion transport in red blood cells, on Ca2(+)-activated Cl- currents (ICl(Ca)) in Xenopus oocytes were examined. Both compounds reversibly inhibited ICl(Ca), elicited in response to depolarizing voltage steps, in a dose-dependent manner, with no effect on the shape of the current-voltage curve. The apparent inhibition constant for niflumic acid was 17 microM, whereas that for flufenamic acid was 28 microM. Niflumic acid also inhibited ICl(Ca) elicited by bath application of Ca2+ to oocytes permeabilized using the Ca2+ ionophore A23187, demonstrating that the inhibition of ICl(Ca) is due to a direct interaction with the Cl- channel, rather than by interference with Ca2+ entry through voltage-dependent Ca2+ channels. In addition to their use in the elimination of ICl(Ca) as a possible source of artifact when Xenopus oocytes are used as an expression system for exogenous ion channels and receptors, it is expected that these two compounds will find use as potent anion channel blockers.