Potassium Homeostasis: The Knowns, the Unknowns, and the Health Benefits

Abstract

Potassium homeostasis has a very high priority because of its importance for membrane potential. Although extracellular K⁺ is only 2% of total body K⁺, our physiology was evolutionarily tuned for a high-K⁺, low-Na⁺ diet. We review how multiple systems interface to accomplish fine K⁺ balance and the consequences for health and disease.

FIGURE 1.

A schematic diagram illustrating three different control mechanisms for ECF K⁺ homeostasis during dietary K⁺ intake Feedback control is driven by a rise of plasma [K⁺], i.e., perturbation of the system, and feedforward control is driven by the sensing of dietary K⁺ intake in the gastrointestinal tract, independent of plasma [K⁺]. Predictive or adaptive control is driven by circadian rhythms.

FIGURE 2.

An overview of K⁺ fluxes (solid arrows) and routes of regulatory cross talk (dotted arrows) between organs during dietary K⁺ intake See text for explanations of individual K⁺ fluxes and regulatory cross talk.

FIGURE 4.

A demonstration of the operation of a feedforward control during normal dietary K⁺ intake in rats Top: a normal, K⁺-containing meal may increase renal K⁺ excretion by increasing plasma [K⁺] and/or activating a feedforward control in response to gut sensing of dietary K⁺ intake. Bottom: when the same but K⁺-deficient meal was given to rats (no gut sensing of dietary K⁺ and thus feedforward control) and plasma [K⁺] was matched by intravenous K⁺ infusion, renal excretion was significantly smaller (69), indicating that a predominant portion of the increase in renal K⁺ excretion during normal dietary K⁺ intake is due to a feedforward control.

FIGURE 3.

Schematic diagram and flow charts illustrating molecular events regulating Na⁺, K⁺, Cl⁻, and H⁺ transport and their transporters A schematic diagram illustrating molecular events regulating Na⁺, K⁺, Cl⁻, and H⁺ transport and their transporters in different regions of the distal nephron (top). Also shown are flow charts showing how these individual molecular events work in concert to regulate K⁺ and Na⁺ excretion in response to low (bottom left) or high (bottom right) plasma [K⁺]. BK, high-conductance Ca²⁺-activated K⁺ channel; CD, collecting duct; CNT, connecting tubule; DCT, distal convoluted tubule; DCT1, the first portion of the DCT; DCT2, the second portion of the DCT; ENaC, epithelial Na⁺ channel; IC, intercalated cells; Kir, inwardly rectifying K⁺ channel; KCC, K⁺-Cl⁻ cotransporter; MR, mineralocorticoid receptor; NCC, Na⁺-Cl⁻ cotransporter; NCC-P, NCC phosphorylation; PC, principal cells; ROMK, renal outer medulla K channel; SGK1, serum- and glucocorticoid-inducible kinase 1; SGK1-P, SGK1 phosphorylation; SPAK, Ste20p-related proline and alanine-rich kinase; SPAK-P, SPAK phosphorylation; TK, tissue kallikrein; V, voltage or membrane potential; WNK, with-no-lysine kinase.