Analysis of Long-Term Potassium Regulation*

Potassium regulation is maintained by a system which affects the rate of renal excretion of the ion and its distribution between the intra- and extracellular spaces. Long-term regulation is accomplished by the interactions of several components of the control system. The direct effect of changes in plasma potassium concentration on potassium secretion by the cells of the distal nephron is the most powerful regulator of K excretion. Changes in aldosterone concentration interact multiplicatively with the effect of plasma K on K excretion, and changes in aldosterone also affect the distribution of the ion so that elevations in aldosterone shift a greater proportion of K into the cells of the body. Sodium intake affects K excretion, increases in intake resulting in a higher rate of K excretion. Aldosterone secretion is regulated by a multiplicative interaction between angiotensin II and potassium concentration. An hypothesis that states in essence that long-term K regulation is determined by the interaction of several component systems is developed. A mathematical model constructed from the hypothesis employing data from experiments designed to quantitatively analyze the functions of the individual components is presented. The model is used to test the hypothesis by comparing the operation of the model with the results of experiments in which the potassium control system is subjected to a wide range of challenges and perturbations. General agreement between model predictions and experimental results was obtained, thereby providing support for the validity of the hypothesis. Building the model drew attention to several areas in which experimental investigation is required to obtain understanding of several important physiological processes. Finally, several predictions obtained from the model may have clinical relevance in the areas of renal medicine and hypertension.