BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion

C Rivera, H Li, J Thomas-Crusells, H Lahtinen, T Viitanen, Avtandil Nanobashvili, Zaal Kokaia, MS Airaksinen, J Voipio, K Kaila, M Saarma

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375 Citations (SciVal)


Pathophysiological activity and various kinds of traumatic insults are known to have deleterious long-term effects on neuronal Cl- regulation, which can lead to a suppression of fast postsynaptic GABAergic responses. Brain-derived neurotrophic factor (BDNF) increases neuronal excitability through a conjunction of mechanisms that include regulation of the efficacy of GABAergic transmission. Here, we show that exposure of rat hippocampal slice cultures and acute slices to exogenous BDNF or neurotrophin-4 produces a TrkB-mediated fall in the neuron-specific K+-Cl- cotransporter KCC2 mRNA and protein, as well as a consequent impairment in neuronal Cl- extrusion capacity. After kindling-induced seizures in vivo, the expression of KCC2 is down-regulated in the mouse hippocampus with a spatio-temporal profile complementary to the up-regulation of TrkB and BDNF. The present data demonstrate a novel mechanism whereby BDNF/TrkB signaling suppresses chloride-dependent fast GABAergic inhibition, which most likely contributes to the well-known role of TrkB-activated signaling cascades in the induction and establishment of epileptic activity.
Original languageEnglish
Pages (from-to)747-752
JournalJournal of Cell Biology
Issue number5
Publication statusPublished - 2002

Subject classification (UKÄ)

  • Neurology


  • neurotrophic factors
  • chloride homeostasis
  • depolarization
  • GABA(A)
  • inhibition
  • hippocampus


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