Nucleic Acids Regulate Intracellular Ions and Membrane Potential

Abstract

The positive charge on the major intracellular inorganic cations (K+, Na+, and Mg2+) significantly exceeds the combined negative charge on Cl- and HCO3-. This so-called anion gap must be balanced by organic anions. From the analysis of published data, we conclude that organic phosphorus-containing compounds (Po) are responsible for the neutralization of much of the anion gap. Importantly, many of them are large polymers, such as DNA, RNA, or polyphosphate, that undergo regular synthesis and degradation. That produces a variable average valency z associated with organic anions. It follows from theory that an increase in z should lead to membrane hyperpolarization and accumulation of cations: this result has been known before, and here we further confirm it by an analysis based on different cellular and computational models. Furthermore, we show that inhibition of potassium channels is expected to reduce the uptake of phosphorus through sodium-coupled transporters. This suggests a simple explanation to two long-established experimental facts about DNA synthesis: namely, that it is accompanied by cell hyperpolarization and that it requires functional potassium channels.