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

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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.

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Abbreviations

DCT:

Distal convoluted tubule

DCT1:

Early distal convoluted tubule

DCT2:

Late distal convoluted tubule

CNT:

Connecting tubule

NCC:

NaCl co-transporter

NKCC:

Na+2Cl−K+ 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

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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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Authors and Affiliations

  1. Medical Cell Biology, University of Regensburg, 93053, Regensburg, Germany

    Sascha Bandulik, Katharina Schmidt, Evelyn Humberg, Richard Warth & Markus Reichold

  2. Great Ormond Street Hospital, Institute of Child Health, UCL, London, NW3 2PF, UK

    Detlef Bockenhauer & Robert Kleta

  3. Department of Neuroscience, Physiology, and Pharmacology, UCL, London, NW3 2PF, UK

    Anselm A. Zdebik & Robert Kleta

  4. Department of Medicine, UCL, London, NW3 2PF, UK

    Detlef Bockenhauer, Anselm A. Zdebik & Robert Kleta

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  1. Sascha Bandulik
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  2. Katharina Schmidt
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  4. Anselm A. Zdebik
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Correspondence to Richard Warth.

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Bandulik, S., Schmidt, K., Bockenhauer, D. et al. The salt-wasting phenotype of EAST syndrome, a disease with multifaceted symptoms linked to the KCNJ10 K+ channel. Pflugers Arch - Eur J Physiol 461, 423–435 (2011). https://doi.org/10.1007/s00424-010-0915-0

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  • DOI: https://doi.org/10.1007/s00424-010-0915-0

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