Dokumentenart: | Artikel | ||||
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Titel eines Journals oder einer Zeitschrift: | Journal of the American Society of Nephrology | ||||
Verlag: | AMER SOC NEPHROLOGY | ||||
Ort der Veröffentlichung: | WASHINGTON | ||||
Band: | 32 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 6 | ||||
Seitenbereich: | S. 1498-1512 | ||||
Datum: | 2021 | ||||
Institutionen: | Biologie und Vorklinische Medizin > Institut für Physiologie > Prof. Dr. Richard Warth | ||||
Identifikationsnummer: |
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Stichwörter / Keywords: | DISTAL CONVOLUTED TUBULE; RECTIFYING K+ CHANNEL; BASOLATERAL MEMBRANE; NACL COTRANSPORTER; POTASSIUM CHANNELS; KIR5.1; MUTATIONS; KIR4.1; EXPRESSION; LOCALIZATION; | ||||
Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 56741 |
Zusammenfassung
Background The transepithelial transport of electrolytes, solutes, and water in the kidney is a well-orchestrated process involving numerous membrane transport systems. Basolateral potassium channels in tubular cells not only mediate potassium recycling for proper Na+,K+-ATPase function but are also involved in potassium and pH sensing. Genetic defects in KCNJ10 cause EAST/SeSAME syndrome, ...
Zusammenfassung
Background The transepithelial transport of electrolytes, solutes, and water in the kidney is a well-orchestrated process involving numerous membrane transport systems. Basolateral potassium channels in tubular cells not only mediate potassium recycling for proper Na+,K+-ATPase function but are also involved in potassium and pH sensing. Genetic defects in KCNJ10 cause EAST/SeSAME syndrome, characterized by renal salt wasting with hypokalemic alkalosis associated with epilepsy, ataxia, and sensorineural deafness. Methods A candidate gene approach and whole-exome sequencing determined the underlying genetic defect in eight patients with a novel disease phenotype comprising a hypokalemic tubulopathy with renal salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. Electrophysiologic studies and surface expression experiments investigated the functional consequences of newly identified gene variants. Results We identified mutations in the KCNJ16 gene encoding KCNJ16, which along with KCNJ15 and KCNJ10, constitutes the major basolateral potassium channel of the proximal and distal tubules, respectively. Coexpression of mutant KCNJ16 together with KCNJ15 or KCNJ10 in Xenopus oocytes significantly reduced currents. Conclusions Biallelic variants in KCNJ16 were identified in patients with a novel disease phenotype comprising a variable proximal and distal tubulopathy associated with deafness. Variants affect the function of heteromeric potassium channels, disturbing proximal tubular bicarbonate handling as well as distal tubular salt reabsorption.
Metadaten zuletzt geändert: 29 Feb 2024 12:37