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The Na–K–Cl Co-transporter in astrocyte swelling

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Abstract

Ion channels, exchangers and transporters are known to be involved in cell volume regulation. A disturbance in one or more of these systems may result in loss of ion homeostasis and cell swelling. In particular, activation of the Na+–K+–Cl− cotransporters has been shown to regulate cell volume in many conditions. The Na+–K+–Cl− cotransporters (NKCC) are a class of membrane proteins that transport Na, K, and Cl ions into and out of a wide variety of epithelial and nonepithelial cells. Studies have established the role of NKCC1 in astrocyte swelling/brain edema in ischemia and trauma. Our recent studies suggest that NKCC1 activation is also involved in astrocyte swelling induced by ammonia and in the brain edema in the thioacetamide model of acute liver failure. This review will focus on mechanisms of NKCC1 activation and its contribution to astrocyte swelling/brain edema in neurological disorders, with particular emphasis on ammonia neurotoxicity and acute liver failure.

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Abbreviations

ALF:

acute liver failure

CaMKII:

calcium/calmodulin-dependent protein kinases II

cAMP:

Cyclic adenosine monophosphate

CHX:

cyclohexamide

H2O2 :

hydrogen peroxide

L-NAME:

L-NG-Nitroarginine methyl ester

MAPKs:

mitogen-activated protein kinases

NCCa-ATP :

SUR1-regulated nonselective cation channel

NCX:

Na+/Ca2+ exchanger

NF-κB:

Nuclear factor-kappaB

NH4 + :

ammonia/ammonium ion

NHE:

Na+/H+ exchanger

NKCC:

Na–K–Cl cotransporter

NO:

nitric oxide

NOS:

nitric oxide synthase

ONS:

oxidative/nitrosative stress

OSR1:

oxidative stress response kinase

PK:

protein kinase

SIN-1:

3-morpholinosydnoimine HCl

SiRNA:

Small interfering RNA

SNAP:

S-nitroso-N-acetyl penicillamine

SPAK:

STE20/SPS-1 related, proline-alanine-rich kinase

TBI:

traumatic brain injury

TBOH:

tert-butylhydroperoxide

WNK1:

WNK lysine deficient protein kinase 1

WNK4:

WNK lysine deficient protein kinase 4

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Acknowledgments

This work was supported by a Merit Review from the Department of Veterans Affairs and by National Institutes of Health Grant DK063311. A.R.J is supported by the American Association for the Study of Liver Disease/American Liver Foundation Grant.

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Authors and Affiliations

  1. Department of Pathology (D-33), University of Miami Miller School of Medicine, P.O. Box 016960, Miami, FL, 33125, USA

    Arumugam R. Jayakumar & Michael D. Norenberg

  2. Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, 33125, USA

    Michael D. Norenberg

  3. Miami VA Medical Center, Miami, FL, 33125, USA

    Michael D. Norenberg

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  1. Arumugam R. Jayakumar
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Correspondence to Arumugam R. Jayakumar.

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Jayakumar, A.R., Norenberg, M.D. The Na–K–Cl Co-transporter in astrocyte swelling. Metab Brain Dis 25, 31–38 (2010). https://doi.org/10.1007/s11011-010-9180-3

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