Action of diphenylamine carboxylate derivatives, a family of non-steroidal anti-inflammatory drugs, on [Ca2+]i and Ca(2+)-activated channels in neurons.
Ca(2+)-activated channels, including Ca(2+)-activated non-selective (CAN) channels and Ca(2+)-activated Cl- channels play important roles in regulating the electrical activity of neurons. No blockers of neuronal CAN channels have been previously reported. We used 2-electrode voltage clamping to measure membrane currents and fura-2 fluorescence imaging to measure [Ca2+]i in molluscan neurons. We show that the diphenylamine carboxylate derivative flufenamate (FFA), but not mefenamate or the parent compound, cause a transient increase in ICAN and a slow outward current, and a maintained increase in [Ca2+]i. We interpret this as a FFA-dependent release of Ca2+ from intracellular stores and Ca2+ influx, [Ca2+]i-dependent activation of the CAN and slow outward currents, and slow FFA-dependent channel block.
Shaw
T
T
Department of Physiology, University of New Mexico School of Medicine, Albuquerque 87131, USA.
Lee
R J
RJ
Partridge
L D
LD
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D003593:Cytoplasm / Q000502:physiology; D005439:Flufenamic Acid / Q000494:pharmacology; D016257:Fura-2; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000378:metabolism; D006372:Helix, Snails; D066298:In Vitro Techniques; D008528:Mefenamic Acid / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D062367:ortho-Aminobenzoates; D008528:Mefenamic Acid; D005439:Flufenamic Acid; C001209:fenamic acid; D002118:Calcium; D016257:Fura-2