Deafness and imbalance associated with inactivation of the secretory Na-K-2Cl co-transporter

@article{Delpire1999DeafnessAI,
  title={Deafness and imbalance associated with inactivation of the secretory Na-K-2Cl co-transporter},
  author={Eric Delpire and Jianming Lu and Roger E. England and Christopher Dull and Tina Thorne},
  journal={Nature Genetics},
  year={1999},
  volume={22},
  pages={192-195}
}
Deafness can result from a variety of gene defects. Some genes involved in the physiology of hearing encode membrane transporters that regulate the ionic composition of the fluid bathing the inner ear. The endolymph is an extracellular fluid with an atypical composition that resembles the intracellular milieu, high in K+ and low in Na+. Recent studies have emphasized the prominent role of K+ channels in endolymph secretion and mechanical transduction. Coupled electroneutral transport of Na+, K… 
Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4
TLDR
It is shown that mice lacking the K+/Cl- (K-Cl) co-transporter Kcc4 (coded for by Slc12a7) are deaf because their hair cells degenerate rapidly after the beginning of hearing.
Barttin increases surface expression and changes current properties of ClC-K channels
TLDR
It is shown that barttin functions as an activator of ClC-K chloride channels, and regulation of a CLC chloride channel by an accessory protein and indicate that Cl C-K activation by barttin is required for adequate tubular salt reabsorption.
Molecular Regulation of Na+-K+-2C1- Cotransporter (NKCC1) and Epithelial Chloride Secretion
TLDR
New molecular evidence indicates that NKCC1 function is regulated in the short and long term at the level of protein phosphorylation, membrane targeting, and gene expression, which may lead to new therapeutic approaches to secretory diarrhea as well as diverse clinical conditions in which cell ion composition is disturbed.
Barttin is a Cl- channel β-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion
TLDR
This work describes the first known β-subunit for CLC chloride channels and reveals that heteromers formed by ClC-K and barttin are crucial for renal salt reabsorption and potassium recycling in the inner ear.
Morphologic Change of the Vestibular Organ in the Na +-K +2 Cl-Cotransporter Deficiency Mouse
TLDR
NA-K-2Cl cotransporter-1 may be essential for maintaining the vestibular morphology and its function in mice and NKCC1 is well expressed in human Vestibular end organs.
Physiology and pathophysiology of SLC12A1/2 transporters
TLDR
This review summarizes information that constitutes consensus in the field, but it also discusses current points of controversy and highlights many unanswered questions.
Mutation of the Na-K-Cl co-transporter gene Slc12a2 results in deafness in mice.
TLDR
It is demonstrated that mutations in the gene encoding the basolateral Na-K-Cl co-transporter Slc12a2 (Nkcc1, mBSC2) cause the deafness observed in sy and sy(ns) mice.
Human and murine phenotypes associated with defects in cation-chloride cotransport.
TLDR
Comparison of human and murine phenotypes associated with loss-of-function mutations in cation-chloride cotransporters indicates important differences in physiology of the two species and provides an important opportunity for detailed physiological and morphological analysis of the tissues involved.
Electroneutral Cation-Chloride Cotransporters in the Central Nervous System
TLDR
The association between loss of function in the K+-Cl− cotransporter KCC3, with a severe peripheral neuropathy associated with agenesis of the corpus callosum, has revealed an unexpected role for K-Cl-cotransport in the development and/or maintenance of both the central and peripheral nervous systems.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 35 REFERENCES
Immunohistochemical Localization of the Na-K-Cl Co-transporter (NKCC1) in the Gerbil Inner Ear
TLDR
The co-expression of NKCC1 and Na,K-ATPase in highly specialized subpopulations of cochlear and vestibular fibrocytes provides further evidence for their role in recycling K+ leaked or effluxed through hair cells into perilymph back to endolymph, as postulated in current models of inner ear ion homeostasis.
The Na-K-Cl cotransporters.
  • M. Haas
  • Biology
    The American journal of physiology
  • 1994
TLDR
This review focuses on recent developments in the identification of Na-K-Cl cotransport proteins in epithelia and on the regulation of epithelial Na- K-Clcotransporter function at cellular and molecular levels.
Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney.
TLDR
Northern blot analysis and in situ hybridization indicate that these transporters are expressed predominantly in kidney with an intrarenal distribution consistent with their recognized functional localization, establishing a new family of Na(+)-(K+)-Cl- cotransporters.
Expression of the Na(+)-K(+)-2Cl- cotransporter BSC2 in the nervous system.
TLDR
The apical localization of the cotransporter in CP epithelium suggests a role for the cotsC2 in cerebrospinal fluid K+ homeostasis and may help regulate intracellular Cl- concentration and thereby affect neuronal response to gamma-aminobutyric acid.
Partial cloning and characterization of Slc12a2: the gene encoding the secretory Na+-K+-2Cl-cotransporter.
TLDR
The Slc12a2 gene encodes a widely expressed bumetanide-sensitive Na+-K+-2Cl-cotransporter that participates in various functions such as Cl- secretion and cell volume regulation and the identification of an alternatively spliced variant of the cotransporter, expressed primarily in brain.
...
1
2
3
4
...