Use of cultured human neuroblastoma cells in rapid discovery of the voltage-gated potassium-channel blockers.
Depolarization of human neuroblastoma cells by high concentrations of extracellular potassium ions, leads to the activation of the voltage-gated potassium channels. The activity of such potassium channels can be effectively and rapidly monitored by tracking the efflux of 86Rb from pre-loaded target cells in response to the depolarizing stimulus. The inclusion of compounds with unknown activity in the assay medium, can result in the identification of novel blockers of the voltage-gated potassium channels. Since this functional assay is performed in 96-well microtitre plates, it represents a rapid and high-volume primary screening method for the detection and identification of the voltage-gated potassium-channel blockers, which may have therapeutic utility in several indications including memory degeneration and cardiac arrhythmias.
Toral
J
J
CV/CNS Research Section, American Cyanamid Company, Lederle Laboratories, Pearl River, New York 10965.
Hu
W
W
Yi
L
L
Barrett
J E
JE
Sokol
P T
PT
Ziai
M R
MR
D015761:4-Aminopyridine / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D018999:Charybdotoxin; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers; D012414:Rubidium Radioisotopes; D012604:Scorpion Venoms / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D026902:Potassium Channel Blockers; D012414:Rubidium Radioisotopes; D012604:Scorpion Venoms; D013757:Tetraethylammonium Compounds; D018999:Charybdotoxin; D001464:Barium; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D011188:Potassium