NS-004 - AN ACTIVATOR OF CA2+-DEPENDENT K+ CHANNELS IN CEREBELLAR GRANULE CELLS

THE large-conductance Ca2+-dependent K+ channels or BK channels in cerebellar granule cells were studied by patch-clamp technique, and the effects on channel activity of the molecule NS 004 (1-(2-hydroxy-5-chlorophenyl)-5-trifiuoromethyl-2-benzimidazolone) were investigated. The channels had a unit conductance of 187 pS, were blocked by charybdotoxin and activated by internal Ca2+. NS 004 (10-30 mu M) significantly increased the single channel opening frequency as well as the mean open time. In whole-cell recordings the compound shifted the BK current-voltage relationship by up to 40 mV towards negative membrane potentials. NS 004 is an efficient BK channel opener, which may represent a novel approach to relaxation of neuronal cells expressing this type of K+ channel.