Two types of chloride transporters are required for GABA A receptor-mediated inhibition in C. elegans

Andrew Bellemer, Taku Hirata, Michael F Romero, Michael R. Koelle

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Chloride influx through GABA-gated Cl - channels, the principal mechanism for inhibiting neural activity in the brain, requires a Cl - gradient established in part by K + -Cl - cotransporters (KCCs). We screened for Caenorhabditis elegans mutants defective for inhibitory neurotransmission and identified mutations in ABTS-1, a Na +-driven Cl - -HCO 3 ' exchanger that extrudes chloride from cells, like KCC-2, but also alkalinizes them. While animals lacking ABTS-1 or the K + -Cl - cotransporter KCC-2 display only mild behavioural defects, animals lacking both Cl - extruders are paralyzed. This is apparently due to severe disruption of the cellular Cl - gradient such that Cl - flow through GABA-gated channels is reversed and excites rather than inhibits cells. Neuronal expression of both transporters is upregulated during synapse development, and ABTS-1 expression further increases in KCC-2 mutants, suggesting regulation of these transporters is coordinated to control the cellular Cl - gradient. Our results show that Na +-driven Cl - -HCO 3' exchangers function with KCCs in generating the cellular chloride gradient and suggest a mechanism for the close tie between pH and excitability in the brain.

Original languageEnglish (US)
Pages (from-to)1852-1863
Number of pages12
JournalEMBO Journal
Volume30
Issue number9
DOIs
StatePublished - May 4 2011

Fingerprint

GABA-A Receptors
Chlorides
gamma-Aminobutyric Acid
Brain
Animals
Caenorhabditis elegans
Extruders
potassium-chloride symporters
Synaptic Transmission
Synapses
Defects
Mutation
2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid

Keywords

  • C. elegans
  • chloride
  • GABA
  • transporter

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Two types of chloride transporters are required for GABA A receptor-mediated inhibition in C. elegans. / Bellemer, Andrew; Hirata, Taku; Romero, Michael F; Koelle, Michael R.

In: EMBO Journal, Vol. 30, No. 9, 04.05.2011, p. 1852-1863.

Research output: Contribution to journalArticle

Bellemer, Andrew ; Hirata, Taku ; Romero, Michael F ; Koelle, Michael R. / Two types of chloride transporters are required for GABA A receptor-mediated inhibition in C. elegans. In: EMBO Journal. 2011 ; Vol. 30, No. 9. pp. 1852-1863.
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