09:05am Wednesday 18 October 2017

Researchers Demonstrate the Existence of Signaling Axis for Control of Potassium Balance

“Potassium is critical to the normal function of the cells of the body,” said Richard A. Preston, M.D., M.S.P.H., M.B.A., professor of medicine and Chief of the Division of Clinical Pharmacology, and lead author of the study. “The body must maintain a normal serum potassium concentration for proper functioning of the heart and internal organs. A high potassium concentration, known as hyperkalemia, can result in abnormal cardiac rhythm and eventually in cardiac arrest.”

The principal method by which the body eliminates excess potassium quickly and efficiently is via the kidney, which excretes potassium into the urine. The increase in serum potassium concentration that follows a potassium-containing meal has traditionally been considered to be the primary determinant of potassium excretion. According to the traditional view, increased potassium concentration directly increases renal potassium excretion by the kidney and also stimulates the hormone aldosterone, which further amplifies potassium excretion. Thus, potassium balance has been classically understood as a negative feedback system determined primarily by an increase in the serum potassium concentration.

“But,” said Preston, “an increase in potassium concentration may not be the only trigger to acutely increase renal potassium excretion. Recent laboratory investigations suggest there is a novel gastrointestinal-renal kaliuretic signaling axis originating in the gastrointestinal tract that directly senses ingested potassium. It signals the kidney to increase renal potassium excretion in response to food intake, prior to an increase in the serum potassium concentration.”

This signaling axis is hypothesized to be mediated by sensors located in the gastrointestinal tract. These sensors detect ingested potassium and rapidly initiate the release or activation of factors that signal the kidney to produce an acute increase in renal potassium excretion.

“The central objective of our study was to investigate the existence and magnitude of this purported gastrointestinal-renal kaliuretic signaling axis in humans,” said Preston. “Our 15-bed inpatient Clinical Pharmacology Research Unit provided the ideal setting for carrying out the complex balance studies required to investigate the physiology of this axis in humans.”

The researchers conducted meal-based potassium-handling experiments in two groups of healthy human volunteers that produced a rapid increase in potassium excretion with no increase in serum potassium concentration. This effect persisted even when the hormone aldosterone, which can also increase potassium excretion, was blocked. The findings suggest that a mechanism for potassium excretion exists independent of the classical physiological pathways.

“Our experiments provide data that support the existence of a novel gastrointestinal-renal kaliuretic signaling axis in humans,” said Preston. “It appears to mediate a significant share of the potassium excretion that follows a complex potassium-containing meal, independent of changes in serum potassium concentration and aldosterone. This axis appears to function alongside the known mechanisms mediated by changes in extracellular potassium concentration, and it may offer an auxiliary alternative mechanism for potassium excretion.”

Miller School of Medicine co-authors of the journal article were David Afshartous, Ph.D., research associate professor, Rolando Rodco, M.D., research associate, and Alberto B. Alonso, M.D., clinical trials manager, all working in the Clinical Pharmacology Research Unit in the Division of Clinical Pharmacology.

Miller School Departments, Centers and Institutes


Share on:
or:

Health news