Tubular Transport II: Potassium

Question 1

Distribution of Potassium in the Body

Answer 1

• [K+]ICF / [K+]ECF determines membrane potential; hence, disturbances in [K+]ECF can have a significant functional impact on excitable cells.

-Example: Alterations in EKG

• [K+]ECF is very closely regulated, averaging 4.2 ± 0.3 mEq/L
• [K+]ECF depends on:
• Total body K+ content (K+ intake – K+ output)
• K+ distribution between ECF and ICF (Na+-K+-ATPase)

Question 2

Hormones that ↑K+ uptake into cells

Answer 2

—Insulin

—β-adrenergic agonists (e.g. epinephrine)

—Aldosterone

Question 3

Acid-base disturbances

Answer 3

• decrease pH –> decrease K+ uptake into cells
• increased pJ –> increased K+ intake into cells

Question 4

Filtration, Reabsorption and Secretion of Potassium

Answer 4

• Freely filtered.
• >90% reabsorbed by proximal tubule & thick ascending limb.
• Secreted by distal tubule & collecting duct.
• Regulation of K+ excretion occurs in distal tubule & collecting duct (achieved by increasing or decreasing the rate of K+ secretion).

Question 5

Mechanisms of Potassium Transport

Answer 5

• Proximal Tubules – passive reabsorption

-H2O reabsorption –> ↑ lumen [K+] –> concentration gradient favoring K+ reabsorption via paracellular pathway

• Loop of Henle (TAL) – active & passive transport

• Apical Na+-K+-2Cl– co-transport –> ↑ intracellular [K+] –> exits basolateral aspect of the cell down its electrochemical gradient (not overly efficient because some K+ can recycle across apical membrane)
• Some crosses the TAL epithelial monolayer with Na+ via paracellular route

• Collecting Tubule and Collecting Duct:

• α-Intercalated cells (ICT, CCT & MCD): active reabsorption (during low dietary K+ intake)

*Apical uptake via H+-K+-ATPase –> ↑intracellular [K+] –> exits cell via basolateral K+ channel

-Principal cells (ICT and CCT): active secretion

*K+ uptake from peritubular interstitium via basolateral Na+-K+-ATPase –> ↑ intracellular [K+] –> passive flux of K+ across apical membrane (probably via a K+ channel)

Question 6

How is normal K+ secretion controlled, under normal circumstances?

Answer 6

• Under most conditions (normal or high dietary K+ intake), K+ excretion is controlled by varying the rate of K+ secretion by the principal cells of the ICT and CCT.
• This occurs entirely as the result of alterations in the electrochemical gradient favoring K+ movement into the tubular fluid, which can occur as follows:
• ↑ Na+-K+-ATPase activity (i.e. increase principal cell [Na+] or the [K+] of ECF –> ↑ intracellular [K+] –> ↑ K+ secretion
• ↑ Tubular fluid flow –> secreted K+ is flushed into downstream segments of the tubule –> maintain [K+] low in tubular lumen –> increase K+ secretion
• ↑ Tubule lumen negativity (i.e. due to stimulation of Na+ reabsorption) –> ↑ electrical gradient favoring K+ secretion

Question 7

Effects of Diuretics on Potassium Excretion

Answer 7

• K+-Wasting Diuretics (e.g. mannitol, furosemide)

-Agents that inhibit Na+ (and H2O) reabsorption by the proximal tubule or loop of Henle –Mechanism: the increased tubular fluid flow rate in the distal tubule and collecting duct promotes K+ secretion.

• K+-Sparing Diuretics (e.g. amiloride, spironolactone)

• Agents that inhibit Na+ (and H2O) reabsorption by the distal nephron (ICT, CCT or collecting duct)
• Mechanism: effect of increased tubular fluid flow on K+ secretion is minimized by the effect of decreased Na+ reabsorption to decrease lumen negativity

Question 8

Physiological Regulation of K+ Excretion

Answer 8

• PK (and, hence, [K+]ECF) is tightly coupled to K+ excretion.
• Mechanisms:
• ↑ Dietary K+ intake –> ↑ [K+]ECF –> increase Na+-K+-ATPase activity –> ↑ K+ uptake across basolateral membrane of distal tubule & collecting duct cells –> ↑ K+ secretion –>↑ K+ excretion.
• ↑ PK –> direct stimulus of aldosterone release (adrenal cortex) –> ↑ apical Na+ entry into CD cells –> ↑ lumen negativity and Na+-K+- ATPase activity –>↑ K+ secretion –> ↑ K+ excretion.