The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation

Claudio Rivera, Juha Voipio, John A Payne, Eva Ruusuvuori, Hannele Lahtinen, Karri Lamsa, Ulla Pirvola, Mart Saarma, Kai Kaila

Research output: Contribution to journalArticlepeer-review

1493 Scopus citations

Abstract

GABA (γ-aminobutyric acid) is the main inhibitory transmitter in-the adult brain, and it exerts its fast hyperpolarizing effect through activation of anion (predominantly Cl-)-permeant GABA(A) receptors. However, during early neuronal development, GABA(A)-receptor-mediated responses are often depolarizing, which may be a key factor in the control of several Ca2+- dependent developmental phenomena, including neuronal proliferation, migration and targeting. To date, however, the molecular mechanism underlying this shift in neuronal electrophysiological phenotype is unknown. Here we show that, in pyramidal neurons of the rat hippocampus, the ontogenetic change in GABA(A)-mediated responses from depolarizing to hyperpolarizing is coupled to a developmental induction of the expression of the neuronal Cl- - extruding K+/Cl- co-transporter, KCC2 (ref. 7). Antisense oligonucleotide inhibition of KCC2 expression produces a marked positive shift in the reversal potential of GABA(A) responses in functionally mature hippocampal pyramidal neurons. These data support the conclusion that KCC2 is the main Cl- extruder to promote fast hyperpolarizing postsynaptic inhibition in the brain.

Original languageEnglish (US)
Pages (from-to)251-255
Number of pages5
JournalNature
Volume397
Issue number6716
DOIs
StatePublished - Jan 21 1999
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'The K<sup>+</sup>/Cl<sup>-</sup> co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation'. Together they form a unique fingerprint.

Cite this