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.