Activation of human IK and SK Ca2+ -activated K+ channels by NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime).
We have identified and characterized the compound NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) as a potent activator of human Ca2+ -activated K+ channels of SK and IK types, whereas it is devoid of effect on BK type channels. IK- and SK-channels have previously been reported to be activated by the benzimidazolinone, 1-EBIO and more potently by its dichloronated-analogue, DC-EBIO. NS309 is at least 1000 times more potent than 1-EBIO and at least 30 times more potent than DC-EBIO when the compounds are compared on the same cell.
Strøbaek
Dorte
D
NeuroSearch A/S, Pederstrupvej 93, DK-2750 Ballerup, Denmark.
Teuber
Lene
L
Jørgensen
Tino D
TD
Ahring
Philip K
PK
Kjaer
Katrine
K
Hansen
Rie S
RS
Olesen
Søren Peter
SP
Christophersen
Palle
P
Skaaning-Jensen
Bo
B
D001562:Benzimidazoles / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D007700:Kinetics; D010091:Oximes / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000378:metabolism; D051640:Small-Conductance Calcium-Activated Potassium Channels
C493327:6,7-dichloro-1H-indole-2,3-dione 3-oxime; D001562:Benzimidazoles; D002120:Calcium Channel Agonists; D007211:Indoles; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D010091:Oximes; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; C053110:benzimidazol-2-one; C102635:1-ethyl-2-benzimidazolinone