Selective activation of Ca(2+)-dependent K+ channels by novel benzimidazolone.
Activators and blockers of specific ion channels are important pharmacological tools for characterizing ion channels and their influence on cell function. The large-conductance Ca(2+)-dependent K+ channel (BK channel) is blocked by peptides such as charybdotoxin and iberiotoxin, but no selective activator of the channel has been described. Here we report single-channel and whole-cell patch-clamp experiments on the specific activation of BK channels in aortic smooth muscle cells with a new heterocyclic molecule, NS 1619 (1-(2'-hydroxy-5'-trifluoromethylphenyl)-5-trifluoromethyl- 2(3H)benzimidazolone). The effect of NS 1619 on the BK channel was dose-dependent, resulting in a shift of the activation curve by up to -50 mV towards negative membrane potentials. The effect was fully reversible and was antagonized by charybdotoxin as well as by tetraethylammonium ions. The compound hyperpolarized the smooth muscle cells. NS 1619 is a selective and new type of K+ channel activator, which may significantly modulate cell excitability.
Olesen
S P
SP
Department of Cellular Biology, NeuroSearch A/S, Glostrup, Denmark.
Munch
E
E
Moldt
P
P
Drejer
J
J
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D002417:Cattle; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D001562:Benzimidazoles; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; C086491:NS 1619; D002118:Calcium