Block of hippocampal CAN channels by flufenamate

Ca2+-activated non-selective cation (CAN) channels are activated by cytopla smic Ca2+ and I-CAN underlies many slow depolarizing processes in neurons i ncluding a putative role in excitotoxicity. CAN channels in many non-neuron al cells are blocked by non-steroidal antiinflammatory drugs that are deriv atives of diphenylamine-2-carboxylate (DPC). The DPC derivative flufenamate (FFA) has a complex effect on certain neurons, whereby it blocks CAN chann els and increases [Ca2+](i). We report here that FFA, but not the parent co mpound, DPC, blocks CAN channels in hippocampal CAl neurons. As was the cas e in other neurons, the effects of FFA are complex and include a maintained rise in [Ca2+](i). Furthermore, the CAN channel blocking ability of FFA pe rsists even when the channels have been potentiated by a Ca2+-dependent pro cess. The use of a CAN channel-blocking drug is important for delineating C AN channel-dependent processes by a Ca and may provide a basis for therapy for CAN channel-dependent events in ischemia. (C) 2000 Elsevier Science B.V . All rights reserved.