Dose-dependent potentiation and inhibition of single Ca2+-activated K+ channels by flufenamic acid.
Using the patch-clamp technique in an inside-out configuration, we studied the action of an antiinflammatory drug, flufenamic acid (FFA), on single large-conductance Ca2+-activated K+ channels in cultured Vero kidney cells. Depending on its concentration, FFA caused either potentiation or inhibition of K(Ca) channel activity of the same channel. Within the concentration ranges of about 5 to 10 microM and of 50 to 500 microM, FFA increased the channel activity; and within the intermediate range of about 10 to 50 microM, FFA inhibited the channels. The effects were only partially reversible. The activating phases were accompanied by an increase in the channel open time and decreases in the channel closed time and slope factor of the Ca2+ concentration-response curve. An apparent dissociation constant of Ca2+ interaction with the channel changed slightly. Possible mechanisms of the FFA effects are discussed.
Kochetkov
K V
KV
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region.
Kazachenko
V N
VN
Marinov
B S
BS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D005439:Flufenamic Acid / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D014709:Vero Cells
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015221:Potassium Channels; D005439:Flufenamic Acid; D002118:Calcium