The surface potential of cellular membranes is an important determinant in the physiological function of the cell. We have investigated a number of factors that affect the surface potential of membranes. We have also modified the theory that has been used to calculate the surface potential, the Gouy-Chapman theory, to account for these factors. Triphosphoinositide lipids in plasma membranes could have up to five negative charges. We previously investigated the interaction of calcium, magnesium, potassium, protons and other cations with triphosphoinositides, and determined the number of cations bound to the lipid under physiologically-relevant conditions. We also investigated proton titration curves of the lipid and found that there was a cooperative interaction between the two monoester groups in the inositol headgroup. We proposed that this interaction could have important consequences in terms of the net charge on the triphosphoinositide lipid under physiological conditions.