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Titolo:
A HYPERPROSTAGLANDIN-E SYNDROME MUTATION IN KIR1.1 (RENAL OUTER MEDULLARY POTASSIUM) CHANNELS REVEALS A CRUCIAL RESIDUE FOR CHANNEL FUNCTION IN KIR1.3 CHANNELS
Autore:
DERST C; WISCHMEYER E; PREISIGMULLER R; SPAUSCHUS A; KONRAD M; HENSEN P; JECK N; SEYBERTH HW; DAUT J; KARSCHIN A;
Indirizzi:
MAX PLANCK INST BIOPHYS CHEM,FASSBERG 11 D-37070 GOTTINGEN GERMANY MAX PLANCK INST BIOPHYS CHEM D-37070 GOTTINGEN GERMANY PHILIPPS UNIV MARBURG,INST PHYSIOL D-35033 MARBURG GERMANY PHILIPPS UNIV MARBURG,DEPT PEDIAT D-35033 MARBURG GERMANY
Titolo Testata:
The Journal of biological chemistry
fascicolo: 37, volume: 273, anno: 1998,
pagine: 23884 - 23891
SICI:
0021-9258(1998)273:37<23884:AHSMIK>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
INWARD-RECTIFIER; K+-CHANNEL; BARTTERS-SYNDROME; CLONING; EXPRESSION; PROTEIN; BRAIN; HYPERCALCIURIA; CHROMOSOME-21; HETEROGENEITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
C. Derst et al., "A HYPERPROSTAGLANDIN-E SYNDROME MUTATION IN KIR1.1 (RENAL OUTER MEDULLARY POTASSIUM) CHANNELS REVEALS A CRUCIAL RESIDUE FOR CHANNEL FUNCTION IN KIR1.3 CHANNELS", The Journal of biological chemistry, 273(37), 1998, pp. 23884-23891

Abstract

Loss of function mutations in kidney Kir1.1 (renal outer medullary potassium channel, KCNJ1) inwardly rectifying, potassium channels can befound in patients suffering from hyperprostaglandin E syndrome (HPS),the antenatal form of Bartter syndrome. A novel mutation found in a sporadic case substitutes an asparagine by a positively charged lysine residue at amino acid position 124 in the extracellular M1-H5 linker region, When heterologously expressed in Xenopus oocytes and mammalian cells, current amplitudes from mutant Kir1.1a[N124K] channels were reduced by a factor of similar to 12 as compared with wild type, A lysineat the equivalent position is present in only one of the known Kir subunits, the newly identified Kir1.3, which is also poorly expressed inthe recombinant system, When the lysine residue in guinea pig Kir1.3 (gpKir1.3) isolated from a genomic library was changed to an asparagine (reverse HPS mutation), mutant channels yielded macroscopic currentswith amplitudes increased B-fold, From single channel analysis it became apparent that the decrease in mutant Kir1.1 channels and the increase in mutant gpKir1.3 macroscopic currents were mainly due to the number of expressed functional channels. Coexpression experiments revealed a dominant-negative effect of Kir1.1a[N124K] and gpKir1.3 on macroscopic current amplitudes when coexpressed with wild type Kir1.1a and gpKir[K110N], respectively. Thus we postulate that in Kir1.3 channels the extracellular positively charged lysine is of crucial functional importance. The HPS phenotype in man call be explained by the lower expression of functional channels by the Kir1.1a[N124K] mutant.

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Documento generato il 29/09/20 alle ore 04:29:54