The pathophysiological and molecular basis of Bartter's and Gitelman's syndromes.
Molecular defects affecting the transport of sodium, potassium and chloride in the nephron through the ROMK K+ channel, Na+/K+/2Cl- cotransporter, the Na+/Cl- cotransporter and chloride channel have been identified in patients with Bartter's and Gitelman's syndromes. Defects of the angiotensin II type I receptor and CFTR have also being described. These defects are simple (i.e., most are single amino acid substitutions) but affect key elements in tubular transport. The simplicity of the genetic defects may explain why the inheritance of these conditions remains unclear in most kindreds (i.e., not just recessive or dominant) and emphasises the crucial importance of the conformational structure of these channels. Application of this molecular information will allow the early genetic identification of patients with these syndromes and enable us to differentiate between the various disorders at a functional level. It may also identify a subgroup in which the heterozygous form may make patients potentially exquisitely sensitive to diuretics.
Bhandari
S
S
School of Biomedical Sciences, Department of Physiology, University of Leeds, UK.
D000471:Alkalosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D018118:Chloride Channels / Q000235:genetics; D002712:Chlorides / Q000652:urine; D005808:Genes, Recessive; D006801:Humans; D007008:Hypokalemia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D009154:Mutation; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000235:genetics; D049992:Sodium Chloride Symporters; D028021:Sodium-Potassium-Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D013577:Syndrome
D002352:Carrier Proteins; D018118:Chloride Channels; D002712:Chlorides; C086989:KCNJ1 protein, human; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D049992:Sodium Chloride Symporters; D028021:Sodium-Potassium-Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor