Two Types Of Chloride Transporters Are Required For GABAA Receptor-Mediated Inhibition In C. elegans

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Dr.. Andrew Bellemer, Assistant Professor, Molecular Neuroscience (Creator)
Institution
Appalachian State University (ASU )
Web Site: https://library.appstate.edu/

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-–HCO3- 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-–HCO3- 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.

Additional Information

Publication
Bellemer, A., Hirata, T., Romero, M., & Kolle, M. (2011). Two Types Of Chloride Transporters Are Required For GABAA Receptor-Mediated Inhibition In C. elegans. The EMBO Journal (2011)30:1852-1863. https://doi.org/10.1038/emboj.2011.83. Publisher version of record available at: https://www.embopress.org/doi/full/10.1038/emboj.2011.83
Language: English
Date: 2011
Keywords
C. elegans, chloride, GABA, transporter

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