Block of cardiac ATP-sensitive K+ channels by external divalent cations is modulated by intracellular ATP: evidence for allosteric regulation of the channel protein

An analysis of the interaction between extracellular divalent cations and the ATP-sensitive potassium channel in single guinea pig ventricular cells revealed that the current through the ATP-sensitive K channel (I-KATP) is blocked by extracellularly-applied Co2+, Cd2+ and Zn2+ in whole-cell patch clamp recording conditions. A few divalent cations inhibit current through I-KATP channels by binding to regions outside the transmembrane electric field. The block interdependence of internal ATP and external divalent cation binding reveal that a modulatory mechanism is possible.