Effects of flunarizine on spontaneous synaptic currents in rat neocortex

Flunarizine, a non-selective blocker of voltage-dependent Ca2+ and Na+ channels, is clinically effective against several neurological disorders, including epilepsy, migraine, and alternating hemiplegia of childhood. We examined the effects of flunarizine on spontaneous postsynaptic currents in acute brain slices maintained in vitro using patch-clamp electrophysiology. Flunarizine significantly attenuated the amplitude of spontaneous currents in pyramidal neurons from juvenile rat neocortex. Flunarizine had no effect on miniature spontaneous events recorded in the presence of tetrodotoxin, a blocker of voltage-dependent sodium channels. In high (9 mM) extracellular potassium, flunarizine reduced the amplitude and frequency of the spontaneous currents. Additionally, dimethyl sulfoxide, the solvent used in our experiments, reduced the amplitude of spontaneous currents, but only in high extracellular potassium. Our data suggest that the clinical activity of flunarizine may in part be a consequence of reducing spontaneous synaptic currents in the neocortex, especially under conditions of heightened neuronal activity.