@entity9475 is an autosomal recessive @entity8 affecting @entity1219 reabsorption in the thick ascending limb of Henle's loop ( @entity26076 ). The aim of this study was to elucidate the functional implications of mutations in the predominant @entity1 @entity19377 isoform in @entity26076 , hROMK2, involved in @entity69594 . cRNA of flag-tagged hROMK2 and eight mutants identified in seven non-related @entity1 was expressed in @entity1238 oocytes. hROMK2 activity was measured by two-electrode voltage-clamp analysis and defined as the @entity8594 -sensitive current at a holding potential of -75 mV. The subcellular localization of hROMK2 in oocytes was studied by immunocytochemistry. Injection of 25 pg hROMK2 cRNA resulted in an inwardly rectifying @entity8594 -sensitive current of 522+/-43 nA ( n=22). The mutants could be divided into three distinct groups. First, at 25 pg injection mutants W80C, @entity69595 and T313/350X exhibited no significant currents and could only be detected intracellularly. Upon 8 ng injection, plasma membrane presence was observed as well as currents up to 60% of wild-type current. Second, mutants @entity69596 and @entity69597 exhibited no @entity8594 -sensitive current, but were present in the plasma membrane at 0.1 ng and 8 ng injection levels. Third, mutants @entity69598 and @entity53767 were detectable on the plasma membrane (0.1 ng) and yielded currents of 98% and 80% of wild-type, respectively, at 25 pg injection. @entity69599 yielded currents that were 45% of wild-type and were detected both on and just below the plasma membrane at 0.1 ng injection. This study has unraveled three distinct mechanisms by which mutations in hROMK2 could impair channel function in @entity9475 . Future experiments on kidney epithelial cell lines will have to confirm this classification, after which specific pharmacological treatments could be considered for each group of mutations.

Functional implications of mutations in the @entity1 renal outer medullary potassium channel (ROMK2) identified in XXXX .

@entity9475 :: ('MESH:D001477', 'Disease') :: ['Bartter syndrome'] @entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity8 :: ('MESH:D007674', 'Disease') :: ['heterogeneous renal tubular disorder'] @entity26076 :: ('6888', 'Gene') :: ['TAL'] @entity1238 :: ('8355', 'Species') :: ['Xenopus laevis'] @entity53767 :: ('c|SUB|A|179|T', 'DNAMutation') :: ['A179T'] @entity1219 :: ('CHEBI:26710', 'Chemical') :: ['NaCl'] @entity69596 :: ('p|SUB|V|53|E', 'ProteinMutation') :: ['V53E'] @entity69595 :: ('p|SUB|V|103|E', 'ProteinMutation') :: ['V103E'] @entity19377 :: ('3758', 'Gene') :: ['ROMK'] @entity69598 :: ('p|SUB|P|91|L', 'ProteinMutation') :: ['P91L'] @entity8594 :: ('MESH:C080430', 'Chemical') :: ['Ba2+'] @entity69594 :: ('MESH:C537653', 'Disease') :: ['Bartter syndrome type II'] @entity69597 :: ('p|SUB|V|296|G', 'ProteinMutation') :: ['V296G'] @entity69599 :: ('p|SUB|S|294|C', 'ProteinMutation') :: ['S294C']
@entity9475 :: (MESH:D001477,Disease) :: ['Bartter syndrome']
