title: Primary aldosteronism and potassium channel mutations.
abstract: OBJECTIVE
  To summarize and discuss data from recent studies implicating mutations in potassium channel genes in the pathogenesis of primary aldosteronism.
  
  
  RESULTS
  Potassium channel gene variants are associated with the primary aldosteronism phenotype in animals (Kcnma1, TASK-1, and TASK-3) and humans (HERG and KCNJ5). Germline KCNJ5 mutations cause bilateral, familial primary aldosteronism with variable severity and genotype:phenotype correlations. Somatic KCNJ5 mutations occur in approximately 40% of aldosterone-producing adenomas, and are associated with younger age, female sex, more severe primary aldosteronism, lack of responsiveness of plasma aldosterone to upright posture, and zona fasciculata histology. Of five so far described, G151R and L168R are by far the most common. KCNJ5 mutations lead to reduced K⁺/Na⁺ channel selectivity and Na⁺ influx, predisposing to cell membrane depolarization, increased calcium influx, increased expression of genes promoting aldosterone synthesis, and increased aldosterone production by adrenocortical cells. How they lead to adrenal cell proliferation and tumor development is less well understood.
  
  
  CONCLUSIONS
  These findings shed considerable light on the pathophysiology of primary aldosteronism with the potential to lead to new diagnostic approaches and treatments.
authors: Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane, Australia. m.stowasser@uq.edu.au
authors: Michael
authors: M
authors: Stowasser
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C000606913:KCNH2 protein, human; C484274:KCNJ5 protein, human; D015221:Potassium Channels