INTERPRETATION OF EXTRAORDINARY KINETICS OF NA-K+-ATPASE BY A PHASE-CHANGE()

We interpret at a molecular level an extraordinary response in the tra nsient 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 partitio n between these states varies with salt concentration. A jump in salt concentration changes the partition of some of the molecules more rapi dly than they interconvert in a steady state at constant salt concentr ation. We propose that interconversion is limited by free volume in th e lipid of the surrounding membrane. This lipid is partitioned into ph ases that vary with salt concentration. Free volume is larger at the i nterface 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 phosphoin termediate states equilibrate more rapidly than at a constant salt con centration. Functional and structural heterogeneity of Na+-K+-ATPase m olecules is discussed.