The binding of potassium to proteins and to nucleic acids best explains the potassium ion content of cells

Abstract

It is generally assumed that the Mg2+ dependent Na+, K+ ATPase “pump” located within the plasma membrane is the primary mechanism responsible for both the generation and the maintenance of the well known intra- to extracellular Na+ -K+ gradients in mammalian cells. This pump operates to pump out cellular Na+ and pump in K + . It is also generally assumed that Na+ and K+ in the cells are free in solution. If these two assumptions are true one would expect that the Na+ content of a post-mitotic tissue cell population should be negatively correlated to and should be a major predictor of K+ content; and that detergent (Brij 58) permeabilization (disruption of the plasma membrane) would allow free passage of Na+ and K+ down their concentration gradients. This would lead to the rapid loss of cellular K+ and to a rapid increase of cellular Na+. Our recent experiments (Cameron et al. 1988) showed that Brij permeabilized cells do not rapidly lose K+ as predicted by the assumption that K+ is free in the cell.If, on the other hand, most of the cellular K+ is bound to proteins (the major source of total cellular sulfur) and to nucleic acids (the major source of total cellular phosphorus) then the S and P content should he positively correlated to and should be the major predictor of K+ content. Analysis of variation in ion and element content of the cytoplasm of many different cardiac myocytes (n = 90) of the ventricle wall by electron probe x-ray microanalysis in thin freeze-dried cryosections allowed a test of this hypothesis (Fig. 1 and Table 1). Multiple regression analysis showed both S and P content to be positively correlated to and the major predictor of cellular K+ content. In normal post-mitotic cardiac myocytes P and S together explained 70-77% of the variation of cellular K+ content. Inclusion of the Na+ content data to the P and S data did not add further to the prediction of K+ content. These results are interpreted to indicate that cells maintain the majority of their K+ bound to protein and to nucleic acid and that “the pump” is not the primary determinant of the maintenance of cellular K+ content.