Mutations in the ROMK gene in antenatal Bartter syndrome are associated with impaired K+ channel function.
Children with the antenatal variant of Bartter syndrome present the typical pattern of impaired salt reabsorption in the thick ascending limb of Henle's loop (TALH) resulting in marked ante- and postnatal salt wasting. In some of these patients mutations in the renal potassium channel ROMK (KCNJ1) have been found. We analyzed the electrophysiological function of five recently described ROMK channel mutations (V72E, D108H, P110L, A198T and V315G). In whole cell patch clamp recordings wildtype rat ROMK1 exhibited K+ currents of >1 nA at a membrane potential of 100 mV when transfected into COS-7 kidney cells. These currents were sensitive to external Ba2+ and internal Mg2+, which are typical features of the inwardly rectifying KIR channel. In contrast mutated ROMK1 cDNAs expressed either no or only infrequently small currents (<200 pA). Loss of tubular K+ channel function probably prevents apical membrane potassium recycling with secondary inhibition of Na-K-2Cl-cotransport in the TALH. We conclude that mutations in the potassium channel ROMK are the primary events causing renal salt wasting in a subset of patients with the antenatal variant of Bartter syndrome.
Derst
C
C
Institute of Physiology, Philipps University, Marburg, Germany.
Konrad
M
M
Köckerling
A
A
Károlyi
L
L
Deschenes
G
G
Daut
J
J
Karschin
A
A
Seyberth
H W
HW
D000293:Adolescent; D000328:Adult; D000818:Animals; D001477:Bartter Syndrome / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005796:Genes; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009154:Mutation; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D013577:Syndrome
D015221:Potassium Channels