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

THE large-conductance Ca2+-dependent K+ channels or BK channels in cer ebellar granule cells were studied by patch-clamp technique, and the e ffects on channel activity of the molecule NS 004 chlorophenyl)-5-trif iuoromethyl-2-benzimidazolone) were investigated. The channels had a u nit conductance of 187 pS, were blocked by charybdotoxin and activated by internal Ca2+. NS 004 (10-30 mu M) significantly increased the sin gle channel opening frequency as well as the mean open time. In whole- cell recordings the compound shifted the BK current-voltage relationsh ip by up to 40 mV towards negative membrane potentials. NS 004 is an e fficient BK channel opener, which may represent a novel approach to re laxation of neuronal cells expressing this type of K+ channel.