Action of diphenylamine carboxylate derivatives, a family of non-steroidal anti-inflammatory drugs, on [Ca2+]i and Ca2+-activated channels in neurons

Department of Physiology, University of New Mexico School of Medicine, Albuquerque 87131, USA.
Neuroscience Letters (Impact Factor: 2.03). 06/1995; 190(2):121-4. DOI: 10.1016/0304-3940(95)11518-2
Source: PubMed


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.

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Available from: Lloyd Donald Partridge, May 04, 2015
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    • "" The LDAP was abolished by bath infusion of 50 ␮M flufenamic acid (FFA). This concentration of FFA has been routinely used to block nonspecific cationic currents (Shaw et al., 1995; Partridge and Valenzuela 2000 "
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    • "In the rat DHNs, the amplitude and/or the duration of the plateau potential were strongly reduced when most of extracellular Na ϩ was replaced by impermeable molecules through the CAN channels (NMDG or choline), or during superfusion with the specific I CAN blocker FFA. FFA, one member of a class of nonsteroidal anti-inflammatory drugs, was shown to affect two calcium-activated conductances in neurons of the snail Helix aspersa (Shaw et al., 1995). It induced a transient increase in I CAN and in a calcium-activated chloride current, consecutive to a rise in intracellular calcium concentration; subsequently, it blocked the two calcium-activated conductances. "
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