The salt-wasting phenotype of EAST syndrome, a disease with multifaceted symptoms linked to the KCNJ10 K+ channel

  • Sascha Bandulik
  • Katharina Schmidt
  • Detlef Bockenhauer
  • Anselm A. Zdebik
  • Evelyn Humberg
  • Robert Kleta
  • Richard Warth
  • Markus Reichold
Invited Review

Abstract

Mutations in the K+ channel gene KCNJ10 (Kir4.1) cause the autosomal recessive EAST syndrome which is characterized by epilepsy, ataxia, sensorineural deafness, and a salt-wasting tubulopathy. The renal salt-wasting pathology of EAST syndrome is caused by transport defects in the distal convoluted tubule where KCNJ10 plays a pivotal role as a basolateral K+ channel. This review on EAST syndrome outlines the molecular aspects of the physiology and pathophysiology of KCNJ10 in the distal convoluted tubule.

Keywords

Kir4.1 Salt-losing syndrome Distal convoluted tubule Channelopathy Potassium channel Kidney K channel Transport Epilepsy 

Abbreviations

DCT

Distal convoluted tubule

DCT1

Early distal convoluted tubule

DCT2

Late distal convoluted tubule

CNT

Connecting tubule

NCC

NaCl co-transporter

NKCC

Na+2ClK+ co-transporter

CaR

Ca2+-sensing receptor

EAST

Epilepsy, ataxia, sensorineural deafness, and a salt-wasting tubulopathy

SeSAME

Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance

Notes

Acknowledgments

The study was supported by the Deutsche Forschungsgemeinschaft, SFB699, to MR and RW. DB is supported by the special trustees of Great Ormond Street Hospital.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sascha Bandulik
    • 1
  • Katharina Schmidt
    • 1
  • Detlef Bockenhauer
    • 2
    • 4
  • Anselm A. Zdebik
    • 3
    • 4
  • Evelyn Humberg
    • 1
  • Robert Kleta
    • 2
    • 3
    • 4
  • Richard Warth
    • 1
  • Markus Reichold
    • 1
  1. 1.Medical Cell BiologyUniversity of RegensburgRegensburgGermany
  2. 2.Great Ormond Street HospitalInstitute of Child Health, UCLLondonUK
  3. 3.Department of Neuroscience, Physiology, and Pharmacology, UCLLondonUK
  4. 4.Department of Medicine, UCLLondonUK

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