Role of the neuronal K-Cl co-transporter KCC2 in inhibitory and excitatory neurotransmission
Front. Cell. Neurosci.. 2012-01-01; 6:
Lire sur PubMed
1. Front Cell Neurosci. 2012 Feb 21;6:5. doi: 10.3389/fncel.2012.00005. eCollection
Role of the neuronal K-Cl co-transporter KCC2 in inhibitory and excitatory
Chamma I(1), Chevy Q, Poncer JC, Lévi S.
(1)INSERM, UMR-839 Paris, France.
The K-Cl co-transporter KCC2 plays multiple roles in the physiology of central
neurons and alterations of its function and/or expression are associated with
several neurological conditions. By regulating intraneuronal chloride
homeostasis, KCC2 strongly influences the efficacy and polarity of the
chloride-permeable γ-aminobutyric acid (GABA) type A and glycine receptor (GlyR)
mediated synaptic transmission. This appears particularly critical for the
development of neuronal circuits as well as for the dynamic control of GABA and
glycine signaling in mature networks. The activity of the transporter is also
associated with transmembrane water fluxes which compensate solute fluxes
associated with synaptic activity. Finally, KCC2 interaction with the actin
cytoskeleton appears critical both for dendritic spine morphogenesis and the
maintenance of glutamatergic synapses. In light of the pivotal role of KCC2 in
the maturation and function of central synapses, it is of particular importance
to understand the cellular and molecular mechanisms underlying its regulation.
These include development and activity-dependent modifications both at the
transcriptional and post-translational levels. We emphasize the importance of
post-translational mechanisms such as phosphorylation and dephosphorylation,
oligomerization, cell surface stability, clustering and membrane diffusion for
the rapid and dynamic regulation of KCC2 function.