WNK4
Encyclopedia
Serine/threonine-protein kinase WNK4 also known as WNK lysine deficient protein kinase 4 or WNK4, is an enzyme
that in humans is encoded by the WNK4 gene
.
. Its primary role in renal physiology is as a molecular switch between the angiontensin II - aldosterone
mediated volume retention and the aldosterone mediated potassium wasting. This is achieved by regulating the sodium-chloride symporter
(NCC), that is uniquely expressed in the distal nephron and is sensitive to thiazide
type diuretics.
Under basal conditions (low circulating Ang II and low Aldosterone), WNK4 will inhibit NCC function. It has been proposed that in the event of hyperkalemia
and an increased secretion of aldosterone (which will upregulate both ENac and ROMK), this inhibition of NCC, will allow an increase in the arrival of sodium to the distal nephron (rich in ENaC
and ROMK
) which will allow the exchange of sodium for potassium ions, thereby reducing plasma potassium levels, without increasing sodium chloride retention (which is always accompanied by volume expansion). Furthermore it has been proposed that in the presence of AngII the WNK4 mediated NCC inhibition will be suppressed thereby increasing sodium-chloride reabsorption in the distal convoluted tubule. This along with the concomitant increase in passive water reabsortion due to the increased salt load in the distal convluted tubule cells will ultimately increase circulating volume.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the WNK4 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
The WNK4 gene encodes a serine-threonine kinase expressed in distal nephronDistal convoluted tubule
The distal convoluted tubule is a portion of kidney nephron between the loop of Henle and the collecting duct system.- Physiology :It is partly responsible for the regulation of potassium, sodium, calcium, and pH...
. Its primary role in renal physiology is as a molecular switch between the angiontensin II - aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
mediated volume retention and the aldosterone mediated potassium wasting. This is achieved by regulating the sodium-chloride symporter
Sodium-chloride symporter
The sodium-chloride symporter is a cotransporter in the kidney which has the function of reabsorbing sodium and chloride ions from the tubular fluid into the cells of the distal convoluted tubule of the nephron.It is a member of the SLC12...
(NCC), that is uniquely expressed in the distal nephron and is sensitive to thiazide
Thiazide
Thiazide is a term used to describe a type of molecule and a class of diuretics often used to treat hypertension and edema ....
type diuretics.
Under basal conditions (low circulating Ang II and low Aldosterone), WNK4 will inhibit NCC function. It has been proposed that in the event of hyperkalemia
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
and an increased secretion of aldosterone (which will upregulate both ENac and ROMK), this inhibition of NCC, will allow an increase in the arrival of sodium to the distal nephron (rich in ENaC
Epithelial sodium channel
The epithelial sodium channel is a membrane-bound ion-channel that is permeable for Li+-ions, protons and especially Na+-ions. It is a constitutively active ion-channel...
and ROMK
ROMK
ROMK is an acronym for the Renal Outer Medullary Potassium channel. This is an ATP-dependent potassium channel that transports potassium out of cells. It plays an important role in potassium recycling in the thick ascending limb and potassium secretion in the cortical collecting duct of the...
) which will allow the exchange of sodium for potassium ions, thereby reducing plasma potassium levels, without increasing sodium chloride retention (which is always accompanied by volume expansion). Furthermore it has been proposed that in the presence of AngII the WNK4 mediated NCC inhibition will be suppressed thereby increasing sodium-chloride reabsorption in the distal convoluted tubule. This along with the concomitant increase in passive water reabsortion due to the increased salt load in the distal convluted tubule cells will ultimately increase circulating volume.