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Two types of chloride transporters are required for GABA A receptor‐mediated inhibition in C. elegans
Author(s) -
Bellemer Andrew,
Hirata Taku,
Romero Michael F,
Koelle Michael R
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.83
Subject(s) - biology , transporter , gabaa receptor , caenorhabditis elegans , receptor , chloride , microbiology and biotechnology , biochemistry , gene , materials science , metallurgy
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.