The ATP-sensitive K+ channel.

A small conductance K+ channel, that is inactivated by ATP, was recently found in the inner membrane of rat liver mitochondria (Inoue et al., 1991). This finding clearly indicates that a variety of K+ channels, showing ATP-sensitivity, are widely distributed. ATP is an important compound in view of its participation in oxidative phosphorylation and as the source of high-energy phosphate for nearly every energy-requiring reaction in the cell. Therefore, it is easy to speculate that transducing the ATP concentration within a cell into an electrical signal is vital for most living cells. The opening of the ATP-sensitive K+ channel by a decrease in the ATP level shifts the membrane potential in a negative direction and in general depresses cell function. The closing of the channel by an increase in ATP depolarizes the membrane and enhances membrane excitability. It might be speculated that a sequence of amino acids common for the binding site of ATP is preserved and combined with different types of K+ channels, so that the gating with ATP is quite similar between different K+ channels, but the conductance properties are different. The large variability in the value of K1/2ATP in the same cells or between different tissues might be due to modulation of the reaction of ATP and the binding site. These ideas will be substantiated by clarifying the molecular structure of the ATP-sensitive K+ channel in the near future. The molecular mechanisms for the selective channel blockers, sulfonylureas, and for the K+ channel openers should also be clarified.