Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2

Claudio Rivera, Juha Voipio, Judith Thomas-Crusells, Hong Li, Z. Emri, Sampsa Sipilä, John A. Payne, Liliana Minichiello, Mart Saarma, Kai Kaila

Research output: Contribution to journalArticle

333 Citations (Scopus)

Abstract

GABA-mediated fast-hyperpolarizing inhibition depends on extrusion of chloride by the neuron-specific K-Cl cotransporter, KCC2. Here we show that sustained interictal-like activity in hippocampal slices downregulates KCC2 mRNA and protein expression in CA1 pyramidal neurons, which leads to a reduced capacity for neuronal Cl- extrusion. This effect is mediated by endogenous BDNF acting on tyrosine receptor kinase B (TrkB), with down-stream cascades involving both Shc/FRS-2 (src homology 2 domain containing transforming protein/FGF receptor substrate 2) and PLCγ (phospholipase Cγ)-cAMP response element-binding protein signaling. The plasmalemmal KCC2 has a very high rate of turnover, with a time frame that suggests a novel role for changes in KCC2 expression in diverse manifestations of neuronal plasticity. A downregulation of KCC2 may be a general early response involved in various kinds of neuronal trauma.

Original languageEnglish
Pages (from-to)4683-4691
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number19
DOIs
Publication statusPublished - May 12 2004

Fingerprint

Down-Regulation
Neurons
Fibroblast Growth Factor Receptors
Cyclic AMP Response Element-Binding Protein
Neuronal Plasticity
src Homology Domains
Pyramidal Cells
Brain-Derived Neurotrophic Factor
Receptor Protein-Tyrosine Kinases
Type C Phospholipases
gamma-Aminobutyric Acid
Chlorides
Proteins
Messenger RNA
Wounds and Injuries
potassium-chloride symporters

Keywords

  • Activity-dependent gene expression
  • BDNF
  • Epilepsy
  • GABAergic transmission
  • Intracellular chloride
  • Neurotrophic factors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2. / Rivera, Claudio; Voipio, Juha; Thomas-Crusells, Judith; Li, Hong; Emri, Z.; Sipilä, Sampsa; Payne, John A.; Minichiello, Liliana; Saarma, Mart; Kaila, Kai.

In: Journal of Neuroscience, Vol. 24, No. 19, 12.05.2004, p. 4683-4691.

Research output: Contribution to journalArticle

Rivera, C, Voipio, J, Thomas-Crusells, J, Li, H, Emri, Z, Sipilä, S, Payne, JA, Minichiello, L, Saarma, M & Kaila, K 2004, 'Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2', Journal of Neuroscience, vol. 24, no. 19, pp. 4683-4691. https://doi.org/10.1523/JNEUROSCI.5265-03.2004
Rivera, Claudio ; Voipio, Juha ; Thomas-Crusells, Judith ; Li, Hong ; Emri, Z. ; Sipilä, Sampsa ; Payne, John A. ; Minichiello, Liliana ; Saarma, Mart ; Kaila, Kai. / Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 19. pp. 4683-4691.
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