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Pharmacological tools to target NKCC1 in brain disorders [PDF]

Trends in Pharmacological Sciences, 2021
The chloride importer NKCC1 and the chloride exporter KCC2 are key regulators of neuronal chloride concentration. A defective NKCC1/KCC2 expression ratio is associated with several brain disorders. Preclinical/clinical studies have shown that NKCC1 inhibition by the United States FDA-approved diuretic bumetanide is a potential therapeutic strategy in ...
Annalisa Savardi, Laura Cancedda, Marco Borgogno   +2 more
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Localization of NKCC1 in the cochlea and morphology of the cochlea in NKCC1-knockout mice

Journal of Huazhong University of Science and Technology [Medical Sciences], 2006
The distribution of the Na-K-2Cl co-transporter (NKCC1) in the cochlear K+ cycling pathway in cochlea and cochlear histological changes in the NKCC1 knockout mice were investigated. By using immunohistochemistry and toluidine blue staining, the localization of NKCC1 in cochlea of the C57BL/6J mice and the cochlear histological changes in the NKCC1 ...
Hanqi, Chu, Hao, Xiong, Xiaoqin, Zhou, Xiaowen, Huang, Liangqiang, Zhou, Yonghua, Cui   +5 more
openaire   +2 more sources

NKCC1 in human diseases: is the SLC12A2 gene haploinsufficient?

American Journal of Physiology-Cell Physiology, 2023
Mutations in the SLC12A2 gene, which encodes the Na-K-2Cl cotransporter-1 (NKCC1), are linked to various conditions such as neurodevelopmental deficits, deafness, and fluid secretion in different epithelia. Cases of complete NKCC1 deficiency in young patients are straightforward, leading to clinical presentations that overlap with the phenotypes ...
Eric Delpire, Rainelli Koumangoye
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Ultrastructure of the inner ear of NKCC1-deficient mice

Hearing Research, 2001
The transduction of the auditory signal is dependent on the flow of ions within the inner ear. We have generated mice deficient in NKCC1, an ion cotransporter that is thought to be involved in the secretion of K+ by the strial marginal cells. Inner ear histology revealed partial to almost total absence of the scala media and collapse of Reissner's ...
A J, Pace, V J, Madden, O W, Henson, B H, Koller, M M, Henson   +4 more
openaire   +2 more sources

NKCC1 transporter facilitates seizures in the developing brain

Nature Medicine, 2005
During development, activation of Cl(-)-permeable GABA(A) receptors (GABA(A)-R) excites neurons as a result of elevated intracellular Cl(-) levels and a depolarized Cl(-) equilibrium potential (E(Cl)). GABA becomes inhibitory as net outward neuronal transport of Cl(-) develops in a caudal-rostral progression.
Volodymyr I, Dzhala, Delia M, Talos, Dan A, Sdrulla, Audrey C, Brumback, Gregory C, Mathews, Timothy A, Benke, Eric, Delpire, Frances E, Jensen, Kevin J, Staley   +8 more
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Kinase docking to NKCC1 is essential for function

The FASEB Journal, 2007
The secretory Na‐K‐2Cl cotransporter, NKCC1, is highly expressed on the basolateral membrane of Cl − ‐secreting epithelia such as salivary, sweat and lacrimal glands as well as lung, stomach, colon, where it participates to salt/fluid secretion.
Kenneth B. Gagnon, Roger England, Eric Delpire   +2 more
openaire   +1 more source

Novel scaffolds of key regulators of NKCC1

The FASEB Journal, 2007
Recent work from our laboratory has identified an association between the widely expressed NKCC1 and two Ste20p‐like serine/threonine kinases, SPAK and OSR1. Activation of the widely expressed NKCC1 is mediated by SPAK/OSR1 phosphorylation.
Kenneth B. Gagnon, Roger England, Lisa Diehl, Eric Delpire   +3 more
openaire   +1 more source

Hypotension inNKCC1null mice: role of the kidneys

American Journal of Physiology-Renal Physiology, 2006
NKCC1 null mice are hypotensive, in part, from the absence of NKCC1-mediated vasoconstriction. Whether these mice have renal defects in NaCl and water handling which contribute to the hypotension is unexplored. Therefore, we asked 1) whether NKCC1 ( −/−) mice have a defect in the regulation of NaCl and water balance, which might contribute to the ...
Susan M, Wall, Mark A, Knepper, Kathryn A, Hassell, Michael P, Fischer, Adetola, Shodeinde, Wonkyong, Shin, Truyen Derek, Pham, Jamie W, Meyer, John N, Lorenz, William H, Beierwaltes, John R, Dietz, Gary E, Shull, Young-Hee, Kim   +12 more
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Alternative renin regulatory pathways and the NKCC1 isoform

American Journal of Physiology-Renal Physiology, 2005
the macula densa is one of the classic regulatory pathways that control the release of renin from the juxtaglomerular cells ([11][1]). It senses the distal luminal NaCl concentration in the thick ascending limb and sends a signal to increase renin secretion in response to sustained decreases ...
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NKCC1 a Regulator of Glioblastoma Progression

Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with poor prognosis despite multimodal therapy. Chloride cotransporters NKCC1 and KCC2 are key regulators of intracellular chloride levels and thereby determine whether GABA acts inhibitory or excitatory.
Anja Thomsen, Diana Freitag, Madlen Haase, Christian Senft, Falko Schwarz, Silke Keiner   +5 more
openaire   +1 more source