LOE 908 blocks delayed rectifier type potassium channels in PC12 cells and cortical neurons in culture.
The effects of (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2- phenyl-N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908) were studied on K+ currents in undifferentiated cells from a phaeochromocytoma cell line (PC12), in cortical neurons from rat in primary culture, in a rat blood lymphoma cell line (RBL-1) and in a kidney cell line (BHK21). In PC12 cells delayed rectifier K+ currents measured in the whole-cell mode of the patch clamp technique were almost completely blocked by 10 microM LOE 908. The IC50 value was 0.7 microM and the Hill coefficient 0.8. After washout of the inhibitor about 80% of the current recovered. In rat cortical neurons in primary culture LOE 908 inhibited tetraethylammonium (TEA, 10 mM)-sensitive delayed rectifying K+ currents (LOE 908: 1 microM, 61 +/- 25% inhibition; 10 microM 103 +/- 19% inhibition). In contrast to the inhibitory action of LOE 908 on delayed rectifying K+ currents, Ca(2+)-activated potassium currents in BHK21 cells were only inhibited by 25 +/- 5% (10 microM LOE 908, n = 5) and no effect of LOE 908 was found on inward-rectifying K+ currents in RBL-1 cells. We conclude that LOE 908 is a K+ channel blocker with selectivity for delayed outward rectifying K+ channels.
Krause
E
E
Physiologisches Institut, Universität des Saarlandes, Homburg/Saar, Germany.
Pfeiffer
F
F
Schmid
A
A
Arndts
D
D
Schulz
I
I
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000166:cytology; D002118:Calcium; D006224:Cricetinae; D051668:Delayed Rectifier Potassium Channels; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating; D007546:Isoquinolines / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000145:classification / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D000081:Acetamides; D051668:Delayed Rectifier Potassium Channels; D007546:Isoquinolines; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C081356:LOE 908; D002118:Calcium