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Neuronal Chloride Transporters in Health and Disease

Genetic and environmental regulators of Kcc2/KCC2 gene expression

Publication ,  Chapter
Yeo, M; Liedtke, W
January 1, 2020

Kcc2 is a highly regulated gene whose expression is confined to the central nervous system (CNS). KCC2 is the primary co-transporter protein that extrudes chloride and maintains low chloride levels in adult neurons. Because Kcc2 expression is critically linked to neuronal chloride ([Cl-]i) homeostasis, Kcc2 gene expression has to occur at the right place and the right time throughout the life of a neuron. Early neurons have low Kcc2 expression and high intracellular chloride levels (120mM and higher) which leads to GABA functioning in an excitatory manner. The depolarizing effects of GABA in CNS neurons during early brain development facilitates neuronal migration and consequently, the basic building plan of the highly complex 3D-structures of the cerebral cortex. In the neurodevelopmental process known as the “chloride shift, " Kcc2 expression increases to reach a maximum level a few weeks after birth (in rodents), at which time virtually all CNS neurons function at steady-state [Cl-]i of <10mM. Maintenance of low [Cl-]i is critical in adult neurons in order to sustain physiologic levels of inhibitory neurotransmission, a critical feature of all neural circuits via maintenance of their excitatory/inhibitory balance. Decreased expression of Kcc2 in mature CNS neurons has been associated and, in some cases, causally linked with diseases characterized by malfunction of inhibitory neural circuits, such as neuropathic pain, epilepsy, traumatic brain and spinal cord injury, psychosis and neurodegeneration. Mechanistic understanding of how Kcc2 gene expression is regulated is therefore essential for understanding how the vertebrate CNS functions, and how it malfunctions in a variety of neurological and psychiatric disorders.

Duke Scholars

DOI

ISBN

9780128153185

Publication Date

January 1, 2020

Start / End Page

307 / 325
 

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Yeo, M., & Liedtke, W. (2020). Genetic and environmental regulators of Kcc2/KCC2 gene expression. In Neuronal Chloride Transporters in Health and Disease (pp. 307–325). https://doi.org/10.1016/B978-0-12-815318-5.00013-3
Yeo, M., and W. Liedtke. “Genetic and environmental regulators of Kcc2/KCC2 gene expression.” In Neuronal Chloride Transporters in Health and Disease, 307–25, 2020. https://doi.org/10.1016/B978-0-12-815318-5.00013-3.
Yeo M, Liedtke W. Genetic and environmental regulators of Kcc2/KCC2 gene expression. In: Neuronal Chloride Transporters in Health and Disease. 2020. p. 307–25.
Yeo, M., and W. Liedtke. “Genetic and environmental regulators of Kcc2/KCC2 gene expression.” Neuronal Chloride Transporters in Health and Disease, 2020, pp. 307–25. Scopus, doi:10.1016/B978-0-12-815318-5.00013-3.
Yeo M, Liedtke W. Genetic and environmental regulators of Kcc2/KCC2 gene expression. Neuronal Chloride Transporters in Health and Disease. 2020. p. 307–325.
Journal cover image

DOI

ISBN

9780128153185

Publication Date

January 1, 2020

Start / End Page

307 / 325