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.