SELECTIVE ACTIVATION OF CA2-DEPENDENT K+ CHANNELS BY NOVEL BENZIMIDAZOLONE()

Activators and blockers of specific ion channels are important pharmac ological tools for characterizing ion channels and their influence on cell function. The large-conductance Ca2+-dependent KC channel (BK cha nnel) is blocked by peptides such as charybdotoxin and iberiotoxin, bu t no selective activator of the channel has been described. Here we re port single-channel and whole-cell patch-clamp experiments on the spec ific activation of BK channels in aortic smooth muscle cells with a ne w heterocyclic molecule, NS 1619 hylphenyl)-5-trinuoromethyl-2(3H)benz imidazolone). The effect of NS 1619 on the BK channel was dose-depende nt, resulting in a shift of the activation curve by up to -50 mV towar ds negative membrane potentials. The effect was fully reversible and w as antagonized by charybdotoxin as well as by tetraethylammonium ions. The compound hyperpolarized the smooth muscle cells. NS 1619 is a sel ective and new type of K+ channel activator, which may significantly m odulate cell excitability.