RT Journal Article
SR Electronic
T1 Stoichiometry of Potassium Channel Opener Action
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1370
OP 1373
DO 10.1124/mol.56.6.1370
VO 56
IS 6
A1 Insa Gross
A1 Andreas Toman
A1 Ingo Uhde
A1 Christina Schwanstecher
A1 Mathias Schwanstecher
YR 1999
UL http://molpharm.aspetjournals.org/content/56/6/1370.abstract
AB Potassium channel openers (KCOs; e.g., P1075, pinacidil) exert their effects on excitable cells by opening ATP-sensitive potassium channels. These channels are heteromultimers composed with a 4:4 stoichiometry of an inwardly rectifying K+ channel subunit plus a regulatory subunit comprising the receptor sites for hypoglycemic sulfonylureas and KCOs (a sulfonylurea receptor). To elucidate stoichiometry of KCO action, we analyzed P1075 sensitivity of channels coassembled from sulfonylurea receptor isoforms with high or low P1075 affinity. Concentration activation curves for cDNA ratios of 1:1 or 1:10 resembled those for channel opening resulting from interaction with a single site, whereas models for activation requiring occupation of two, three, or four sites were incongruous. We conclude KCO-induced channel activation to be mediated by interaction with a single binding site per tetradimeric complex.