Studies have been made on the cation transport system of the dog red cell, a system of particular interest because it has been shown that there is a marked dependence of cation fluxes on the cell volume. We have found that a 10% decrease in cell volume causes a large increase in 1 hr uptake of 24Na as well as a considerable inhibition of 42K uptake. This effect cannot be produced by a difference in medium osmolality but rather requires the cell volume to change. Dog red cell uptake of 24Na is not inhibited by iodoacetate. Phloretin inhibits 24Na uptake and lactate production, and virtually abolishes the volume effect on Na uptake. These several observations may be accounted for in terms of a working hypothesis which presupposes a cation carrier complex which pumps K into and Na out of cells of normal volume. When the cells are shrunken the carrier specificity shifts to an external Na-specific mode and there is a large increase in 24Na uptake, driven by the inwardly directed Na electrochemical potential gradient.

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