Regulation of Potassium Balance

intracellular v extracellular K

Nernst equation

potassium in diet

-abundant

-since all cells, plants and animal alike, have a high intracellular K

many observational studies show that a high K diet associated with

-lower bp, stroke, and decreased cardiovascular morbidity and mortality

____ is an important determinant of serum K in the steady state

-dietary K

an increase in dietary K is

-excreted rapidly

aldosterone production

-produced in the zona glomerulosa

-angiotensin II (and high plasma K) depolarize the membrane leading to open Ca channels high cell Ca induces aldosterone synthase

disposal of ingested K

-occurs by re-distribution into the intracellular space and by renal excretion

disposal of an ingested K load occurs by

-re-distribution and by urinary excretion

K filtering

-freely filtered

->95% of filtered K is reabsorbed in the proximal tubule and thick ascending limb

-what appears in the urine is secreted by the distal tubule and collecting duct

K secretion in collecting duct

driving forces for K secretion in collecting duct

2 types of K channels mediate K secretion

1) ROMK: small conductance channel

2) BK: large conductance, calcium sensitive

K secretion (and excretion) depends on

-urine flow rate

BK potassium channels

-expressed in many epithelial cells including principal cells and intercalated cells (they are responsible for flow dependent K secretion)

-characteristics: 2 subunits- alpha is the channel, beta a regulator and expressed in different cell types; activated by an increase in intracellular calcium; specifically blocked by iberiotoxin (red scorpion)

flow dependent K secretion

-knockout of BK channels in intercalated cells abolishes flow dependent K secretion

-BK potassium channels respond to flow

how does flow affect K secretion?

-BK channels composed of alpha subunit and 1 of 4 beta subunits

-beta subunits increase the calcium sensitivity

flow dependent K secretion

-high urine flow increases intracellular calcium in both principal and intercalated cells

-BK channels are calcium-activated K channels

how does high flow rate increase cell calcium?

flagella and cilia

-contains close to 400 proteins

-mutations of many of these genes lead to a variety of cystic kidney diseases

-also many other organ specific disease “ciliopathies”

-cortical collecting tubule in the kidney

-showing principal (with flagella) and intercalated cells (*)

how does high flow rate increase cell calcium?

increased flow rate increases

-cell Ca2+ due to stimulation of the cilium in both principal cells and intercalated cells

secretion and reabsorption of K

regulation of K secretion

approach to patient with K disorders

redistribution of K between ECF and ICF

-insulin

-acid base balance

-epinephrine

driving forces for K secretion in collecting duct

hypokalemia

hyperkalemia

clinical manifestations of hypokalemia

-muscle weakness: eventually paralysis; occasionally rhabdomyolysis

-cardiac arrhythmias

clinical manifestations of hyperkalemia

-cardiac arrhythmia

hypokalemia genetic syndromes

hyperkalemia genetic syndromes

thick ascending limb- Bartter’s syndrome

hyperaldosteronism

-secondary: high renin- high angiotensin II states volume depletion, CHD, cirrhosis

-primary: adrenal adenoma, adrenal hyperplasia

aldosterone and K- reciprocal regulation

-aldosterone synthesized only in the zona glomerulosa

mutations in KCNJ5, Ca channels