Mechanisms of type I and type II pseudohypoaldosteronism.
Pseudohypoaldosteronism (PHA) types I and II are curious genetic disorders that share hyperkalemia as a predominant finding. Together they have become windows to understanding new molecular physiology in the kidney. Autosomal recessive PHAI results from mutations in the epithelial sodium channel (ENaC), whereas autosomal dominant PHAI is characterized by mutations in the mineralocorticoid receptor. PHAII is the result of mutations in a family of serine-threonine kinases called with-no-lysine kinases (WNK)1 and WNK4. WNK4 negatively regulates the NaCl cotransporter (NCC), and PHAII mutations in WNK4 abrogate this affect. WNK4 also regulates the expression or function of renal outer medullary potassium (ROMK) channels, ENaCs, and Cl transporters. WNK1 also regulates NCC and ROMK. Aldosterone inactivates WNK1 and WNK4 activity. Whether angiotensin II can fine tune the actions of aldosterone is still unclear.
Furgeson
Seth B
SB
Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado-Denver, 12700 E. 19th Avenue, C281, Aurora, CO 80045, USA.
Linas
Stuart
S
D053503:Epithelial Sodium Channels / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D009154:Mutation / Q000235:genetics; D015221:Potassium Channels / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011546:Pseudohypoaldosteronism / Q000235:genetics* / Q000378:metabolism; D000076204:WNK Lysine-Deficient Protein Kinase 1
D053503:Epithelial Sodium Channels; D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D015221:Potassium Channels; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human; C433806:WNK4 protein, human