NS 004--an activator of Ca(2+)-dependent K+ channels in cerebellar granule cells.
The large-conductance Ca(2+)-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-trifluoromethyl-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 microM) 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.
Olesen
S P
SP
Department of Cellular Biology, NeuroSearch A/S, Glostrup, Denmark.
Munch
E
E
Wätjen
F
F
Drejer
J
J
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018999:Charybdotoxin; D002733:Chlorophenols / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D012604:Scorpion Venoms / Q000494:pharmacology
D001562:Benzimidazoles; D002733:Chlorophenols; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; C083230:NS 004; D002118:Calcium