ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Kinases SPAK and OSR1 are upregulated by estradiol and activate NKCC1 in the developing hypothalamus.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.International journal of molecular sciences · 2023Review
- Maternal taurine as a modulator of ClFrontiers in cellular neuroscience · 2023Review
- The Alteration of Chloride Homeostasis/GABAergic Signaling in Brain Disorders: Could Oxidative Stress Play a Role?Antioxidants (Basel, Switzerland) · 2021Review
- Targeting the WNK-SPAK/OSR1 Pathway and Cation-Chloride Cotransporters for the Therapy of Stroke.International journal of molecular sciences · 2021Review
- Multi-Tissue Multi-Omics Nutrigenomics Indicates Context-Specific Effects of Docosahexaenoic Acid on Rat Brain.Molecular nutrition & food research · 2020Article
- Androgens and the developing hippocampus.Biology of sex differences · 2020Review
- Roles of Testosterone and Estradiol in Mediation of Acute Neuroendocrine and Electroencephalographic Effects of Sevoflurane During the Sensitive Period in Rats.Frontiers in endocrinology · 2020Article
- Sex-Dependent Signaling Pathways Underlying Seizure Susceptibility and the Role of Chloride Cotransporters.Cells · 2019Review
- Sex differences and estrogen regulation of BDNF gene expression, but not propeptide content, in the developing hippocampus.Journal of neuroscience research · 2017Article
- Role of Steroids in Hyperexcitatory Adverse and Anesthetic Effects of Sevoflurane in Neonatal Rats.Neuroendocrinology · 2016Article
- Investigating the stress attenuating potential of furosemide in immobilization and electric foot-shock stress models in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- Development and regulation of chloride homeostasis in the central nervous system.Frontiers in cellular neuroscience · 2015Review
- Article
- Age- and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters.Frontiers in cellular neuroscience · 2015Article
- Structural and biochemical insights into the activation mechanisms of germinal center kinase OSR1.The Journal of biological chemistry · 2014Article
- GABAergic transmission to kisspeptin neurons is differentially regulated by time of day and estradiol in female mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Using sex differences in the developing brain to identify nodes of influence for seizure susceptibility and epileptogenesis.Neurobiology of disease · 2014Review
- Steroid 5α-reductase in adult rat brain after neonatal dihydrotestosterone administration.Neurochemical research · 2013Article
- SPAK differentially mediates vasopressin effects on sodium cotransporters.Journal of the American Society of Nephrology : JASN · 2013Article
- Molecular physiology of SPAK and OSR1: two Ste20-related protein kinases regulating ion transport.Physiological reviews · 2012Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
In immature neurons the amino acid neurotransmitter, GABA provides the dominant mode for neuronal excitation by inducing membrane depolarization due to Cl(-) efflux through GABA(A) receptors (GABA(A)Rs). The driving force for Cl(-) is outward because the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) elevates the Cl(-) concentration in these cells. GABA-induced membrane depolarization and the resulting activation of voltage-gated Ca(2+) channels is fundamental to normal brain development, yet the mechanisms that regulate depolarizing GABA are not well understood. The neurosteroid estradiol potently augments depolarizing GABA action in the immature hypothalamus by enhancing the activity of the NKCC1 cotransporter. Understanding how estradiol controls NKCC1 activity will be essential for a complete understanding of brain development. We now report that estradiol treatment of newborn rat pups significantly increases protein levels of two kinases upstream of the NKCC1 cotransporter, SPAK (STE20/SPS1-related proline alanine rich kinase) and OSR1 (oxidative stress response kinase). The estradiol-induced increase is transcription dependent, and its time course parallels that of estradiol-enhanced phosphorylation of NKCC1. Antisense oligonucleotide-mediated knockdown of SPAK, and to a lesser degree of OSR1, precludes estradiol-mediated enhancement of NKCC1 phosphorylation. Functionally, knockdown of SPAK or OSR1 in embryonic hypothalamic cultures diminishes estradiol-enhanced Ca(2+) influx induced by GABA(A)R activation. Our data suggest that SPAK and OSR1 may be critical factors in the regulation of depolarizing GABA-mediated processes in the developing brain. It will be important to examine these kinases with respect to sex differences and developmental brain anomalies in future studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.