The movement of K+ across the apical membrane is driven by the electrochemical gradient for K+ channels and the chemical concentration gradient for the K+/Cl− symporter. The permeability of apical membrane K+ channels to K+ plays a role in K+ secretion by principal cells. α-Intercalated cells reabsorb K+ through a H+, K+-ATPase transport mechanism located in the apical membrane. This mechanism allows for the exchange of K+ uptake across the apical plasma membrane for H+. K+ exit from intercalated cells into the blood is facilitated by a K+ channel. Reabsorption of K+ is activated by a low-K+ diet. The regulation of K+ secretion in the distal tubule and collecting duct primarily occurs through changes in K+ secretion by principal cells. The main physiological regulators of K+ secretion are plasma [K+] and aldosterone. Ingesting a K+-rich meal also stimulates renal K+ excretion through an unknown gut-dependent mechanism. While arginine vasopressin (AVP) can stimulate K+ secretion, it is less significant compared to plasma [K+] and aldosterone. Other factors such as the flow rate of tubular fluid and acid-base balance can influence K+ secretion in the distal tubule and collecting duct, but they are not involved in homeostatic mechanisms as they disrupt K+ balance. Plasma [K+] is an important factor in determining K+ secretion in the distal tubule and collecting duct. Hyperkalemia resulting from a high-K+ diet or rhabdomyolysis can affect K+ secretion. The cellular mechanism of K+ secretion by principal cells involves the regulation of K+ secretion at various points. Aldosterone has five effects on the secretion of K+ by principal cells in the late segment of the distal tubule and collecting duct. The effects include increasing K+ permeability, the activity of the Na+,K+-ATPase, Na+ entry through the Na+ channel (ENaC), and K+ uptake through the apical K+ channel. Hyperkalemia stimulates the secretion of K+ through various mechanisms such as increasing Na+, K+-ATPase activity, increasing K+ permeability of the apical membrane, stimulating aldosterone secretion, and increasing the flow rate of tubular fluid.
the driving force (electrochemical gradient for K+ channels and the chemical concentration gradient for the K+/Cl− symporter) for movement of K+ across the apical membrane 3.
the permeability of apical membrane K+ channels to K+ Every change in K+ secretion by principal cells results from an alteration in one or more of these factors (Fig. 36.6 α-Intercalated cells reabsorb K+ by a H+ , K+-ATPase transport mechanism (HKA) located in the apical membrane (see
Fig. 36.5B ). This transporter mediates K+ uptake across the apical plasma membrane in exchange for H+ . K+ exit from intercalated cells into the blood is mediated by a K+ channel. Reabsorption of K+ is activated by a low-K+ diet.
Regulation of K+ Secretion by the Distal Tubule and Collecting Duct
Regulation of K+ excretion is achieved mainly by alterations in K+ secretion by principal cells of the late segment of the distal tubule and collecting duct. Plasma [K+] and aldosterone are the major physiological regulators of K+ secretion. Ingestion of a K+-rich meal also stimulates renal K+ excretion by a mechanism involving an unknown gut-dependent mechanism. Arginine vasopressin (AVP), also stimulates K+ secretion; however, it is less important than plasma [K+] and aldosterone. Other factors, including the flow rate of tubular fluid and acid-base balance, influence secretion of K+ by the distal tubule and collecting duct. However, they are not homeostatic mechanisms, because they disturb K+ balance (
Box 36.2
Plasma [K+] is an important determinant of K+ secretion by the distal tubule and collecting duct. Hyperkalemia (e.g., resulting from a high-K+ diet or from rhabdomyolysis)
Fig. 36.6 Cellular mechanism of K+ secretion by principal cells. The numbers indicate where K+ secretion is regulated. 1, Na+,K+-ATPase; 2, electrochemical gradient of K+ across the apical membrane; 3, permeability of the apical membrane to K+ .
Fig. 36.7 Effects of aldosterone on secretion of K+ by principal cells in the late segment of the distal tubule and collecting duct. Numbers refer to the five effects of aldosterone discussed in text.
K+ K+ ˜ K+ permeability + ˜ CAP ˜ SGK˜ ENaC ˜Na+,K+-ATPase + + Na+ ATP 2 1 3 4 5
IN THE CLINIC • BOX 36.2 Major Factors and Hormones Influencing K+Excretion
Physiological: Keep K+ Balance Constant
Pathophysiological: Displace K+ Balance
Flow rate of tubule fluid Acid-base disorders Glucocorticoids stimulates secretion of K+ within minutes. Several mechanisms are involved. First, hyperkalemia stimulates Na+ , K+-ATPase and thereby increases K+ uptake across the basolateral membrane. This uptake raises intracellular [K+] and increases the electrochemical driving force for exit of K+ across the apical membrane. Second, hyperkalemia also increases the permeability of the apical membrane to K+ . Third, hyperkalemia stimulates secretion of aldosterone by the adrenal cortex, which as discussed later, acts synergistically with plasma [K+] to stimulate secretion of K+ . Fourth, hyperkalemia also increases the flow rate of tubular fluid, which as discussed later, stimulates secretion of K+ by the distal tubule and collecting duct.