Analysis of ion channels by modeling the osmotic effects of weak acids and bases

This paper describes computer programs which may be used to identify and analyze cation and anion channels. Weak acids are used to increase intracellular proton concentrations and by so doing to promote the exchange of osmotically active cations with protons. The time course of cation exchange is readily identified from the changes in cell volume which accompany the net changes in osmotically active cations. Weak bases are used to identify and analyze hydroxyl/anion exchange by a comparable strategy. The model was able to produce data that agreed with experimental data in the literature with an accuracy equal to experimental error. One program, called PROPIONATE, uses the weak acid, propionic acid, to identify cation channels such as the sodium-proton exchanger or the calcium-dependent, potassium channel. A second program, called BASE, is more general because either a weak acid such as propionic acid or a weak base such as ammonia may be used individually or together. When experimental data are available, the programs may be used to calculate permeability coefficients for ion channels and the capacity of intracellular buffers. The programs may be used also in the design of experiments. Initial values may be assigned to intracellular and extracellular electrolyte and proton concentrations. Values for intracellular buffer capacity and channel permeabilities may be chosen. The program will then generate changes in ions, cell volume, and intracellular pH when either a weak acid, a weak base or combination of the two is added to the external medium.