TY - JOUR
T1 - Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2
AU - Rivera, Claudio
AU - Voipio, Juha
AU - Thomas-Crusells, Judith
AU - Li, Hong
AU - Emri, Zsuzsa
AU - Sipilä, Sampsa
AU - Payne, John A
AU - Minichiello, Liliana
AU - Saarma, Mart
AU - Kaila, Kai
PY - 2004/5/12
Y1 - 2004/5/12
N2 - 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.
AB - 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.
KW - Activity-dependent gene expression
KW - BDNF
KW - Epilepsy
KW - GABAergic transmission
KW - Intracellular chloride
KW - Neurotrophic factors
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UR - http://www.scopus.com/inward/citedby.url?scp=2442707888&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.5265-03.2004
DO - 10.1523/JNEUROSCI.5265-03.2004
M3 - Article
C2 - 15140939
AN - SCOPUS:2442707888
VL - 24
SP - 4683
EP - 4691
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 19
ER -