Abstract: AIM: To study the effects and mechanisms of ATP-sensitive potassium channel (K_ATP) opener iptkalim (IPT) on the glutamate release from cultured PC12 cells induced by high K +. METHODS: The glutamate release from cultured PC12 cells was measured by using HPLC combined with fluorescent detector analysis. RESULTS: Different concentrations of IPT (0.01, 0.10, 1.00, 10.0, 100 μmol·L -1) were shown to inhibit glutamate release from PC12 cells induced by high K + in a concentration-dependent manner, and these inhibitory effects were partly reversed by K_ATP blocker glibenclamide (Gli), an inhibitor of K_ATP channel.Incubation with 1.00 μmol·L -1 Gli alone increased the glutamate release induced by high K +, but selective PKC inhibitor HA-100 and calmodulin (CaM) antagonist trifluoperazine failed to affect the increment of glutamate release. CONCLUSION: Inhibition of glutamate release by IPT is partly reversed by Gli, indicating that the effect of IPT is mediated by the opening of the K_ATP channel;PKC and CaM are not involved in the increment of glutamate release by Gli.These results demonstrate that K_ATP channel is implicated in modulating glutamate release.

Key words: pharmacology, HPLC, iptkalim, ATPsensitive potassium channel, PC12 cells, glutamate, calmodulin, glibenclamide