Interpretation of extraordinary kinetics of Na(+)-K(+)-ATPase by a phase change.

We interpret at a molecular level an extraordinary response in the transient kinetics of the phosphointermediate of Na(+)-K(+)-ATPase (I. Klodos, R. L. Post, and B. Forbush III. J. Biol. Chem. 269: 1734-1743, 1994). The phosphointermediate comprises two principal states. The partition between these states varies with salt concentration. A jump in salt concentration changes the partition of some of the molecules more rapidly than they interconvert in a steady state at constant salt concentration. We propose that interconversion is limited by free volume in the lipid of the surrounding membrane. This lipid is partitioned into phases that vary with salt concentration. Free volume is larger at the interface between these phases than within the phases themselves. Na(+)-K(+)-ATPase molecules are distributed at random in the membrane. When the phase boundary moves in response to a jump in salt concentration, it crosses some Na+ -K+ -ATPase molecules, which transiently experience an increase in free volume of the surrounding lipid. Thus their phosphointermediate states equilibrate more rapidly than at a constant salt concentration. Functional and structural heterogeneity of Na(+)-K(+)-ATPase molecules is discussed.