Membrane ion transport in Bartter's syndrome: evidence for a new syndrome subtype.

Fifteen patients with Bartter's syndrome (hyponatremic hypochloremic hypokalemic metabolic alkalosis) were compared with 15 healthy volunteers. Red blood cell Na+/H+ and Cl-/HCO3- exchanges were enhanced in all patients with Bartter's syndrome. In calciuric normomagnesemic patients, sensitive to nonsteroidal anti-inflammatory drugs (classic Bartter's syndrome), red blood cell Na+,K+,2Cl- cotransport was markedly reduced, calcium-dependent K+ permeability was moderately increased, and up to 60% of sodium permeability was represented by cAMP-activated fraction (presumably human analog of beta-isoform of Na+/H+ exchange). In noncalciuric hypomagnesemic patients insensitive to indomethacin (Gitelman's syndrome), Na+,K+,2Cl- cotransport was enhanced, Na+ permeability was increased due to calmodulin-dependent fraction, and calcium-dependent K+ permeability was markedly enhanced. A new subtype of Bartter-like syndrome ("variant Bartter's syndrome") has been described in which calciuria, hypomagnesemia, and insensitivity to nonsteroidal anti-inflammatory drugs were associated with decreased Na+,K+,2Cl- cotransport, enhanced calmodulin-activated fraction of Na+ influx, and reduced calcium-dependent K+ permeability.