Negative cooperativity may explain flat concentration-response curves of ATP-sensitive potassium channels.
Blockage of ATP-sensitive K+ channels by various drugs has been reported to exhibit a weak concentration dependence with Hill coefficients below unity. This phenomenon is interpreted by a negative cooperativity between K+ channels whereby drug binding to one channel lowers the drug affinities of neighbouring channels. Results are presented for a dimeric and a tetrameric channel model and compared with published experimental data.
Hehl
S
S
I. Physiologisches Institut, Universität des Saarlandes, Homburg/Saar, Germany.
Neumcke
B
B
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D004563:Electrochemistry; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D014044:Tolbutamide / Q000378:metabolism / Q000494:pharmacology
D007473:Ion Channels; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D014044:Tolbutamide