Potassium homeostasis: sensors, mediators, and targets

Transmembrane potassium (K) gradients are key determinants of membrane potential that can modulate action potentials, control muscle contractility, and influence ion channel and transporter activity. Daily K intake is normally equal to the amount of K in the entire extracellular fluid (ECF) creating a critical challenge - how to maintain ECF [K] and membrane potential in a narrow range during feast and famine. Adaptations to maintain ECF [K] include sensing the K intake, sensing ECF [K] vs. desired set-point and activating mediators that regulate K distribution between ECF and ICF, and regulate renal K excretion. In this focused review, we discuss the basis of these adaptions, including (1) potential mechanisms for rapid feedforward signaling to kidney and muscle after a meal (before a rise in ECF [K]), (2) how skeletal muscles sense and respond to changes in ECF [K], (3) effects of K on aldosterone biosynthesis, and (4) how the kidney responds to changes in ECF [K] to modify K excretion. The concepts of sexual dimorphisms in renal K handling adaptation are introduced, and the molecular mechanisms that can account for the benefits of a K-rich diet to maintain cardiovascular health are discussed. Although the big picture of K homeostasis is becoming more clear, we also highlight significant pieces of the puzzle that remain to be solved, including knowledge gaps in our understanding of initiating signals, sensors and their connection to homeostatic adjustments of ECF [K].

Automated summary

This article discusses the adaptive mechanisms involved in maintaining extracellular potassium concentration and membrane potential stability, including the signaling mechanisms in muscles and kidneys, the sensing and regulation of potassium concentration in skeletal muscles, the effects of potassium on aldosterone synthesis, and the kidney's response to changes in potassium concentration. The concept of sexual dimorphisms in renal potassium handling adaptation is introduced, and the molecular mechanisms underlying the cardiovascular benefits of a potassium-rich diet are discussed.