An index to quantify the apparent regulation of orthophosphate concentration in mammalian cells

Abstract

We have shown previously that the concentration of orthophosphate (P,) in human erythrocytes and skeletal muscle is regulated in response to changes in the extracellular Pi concentration (Bevington et al., 1986). This is in marked contrast to earlier reports that P, simply distributes passively between mammalian cells and extracellular fluid (Deuticke, 1967; Tenenhouse & Scriver, 1975). To compare the extent of regulation of the cellular PI concentration between cell types or in a given cell type under a series of different conditions, some convenient method is needed to quantify the regulation. Wc therefore propose the following phosphate regulation index, p . If the relationship between the extracellular P, concentration (C, in mmol/l) and the cellular P, concentration (C,) is approximately linear, so that Cz = a + bC,, p is taken to be the ratio of the steady-state cellular P, concentration when C , = 0 to the cellular Pi concentration when C , = 1 mM, so that p = a / ( a + 6 ) . The value of 1 mM is chosen for the second extracellular P, concentration as this is approximately the concentration in normal human extracellular fluid. This index has some useful properties. In a cell which can regulate its P, concentration perfectly so that C', is constant as C, varies, p = 1; whereas in a cell in which P, is passively distributed so that C, is directly proportional to C,, p = 0. A furthcr advantage is that p is the ratio of two cellular P, concentrations, so that it is independent of the units in which the concentrations are expressed (e.g. mmol/l of cell water, or pmol/mg of protein). In Table 1 we summarize 10 published studies of the relationship betwecn C, and C, from which values of p can be derived. In seven of the 10 studies the relationship deviates markedly from that expected if P, distributes passively (because p 0.4). In -human erythrocytes, p seems to depend on the precise conditions under which it is measured.