The Possium Chloride Cotransporter KCC-2 Coordinates Development Of Inhibitory Neurotransmission And Synapse Structure In Caenorhabditis 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 chloride channels, the primary mechanism by which neural activity is inhibited in the adult mammalian brain, depends on chloride gradients established by the potassium chloride cotransporter KCC2. We used a genetic screen to identify genes important for inhibition of the hermaphrodite-specific motorneurons (HSNs) that stimulate Caenorhabditis elegans egg-laying behavior and discovered mutations in a potassium chloride cotransporter, kcc-2. Functional analysis indicates that, like mammalian KCCs, C. elegans KCC-2 transports chloride, is activated by hypotonic conditions, and is inhibited by the loop diuretic furosemide. KCC-2 appears to establish chloride gradients required for the inhibitory effects of GABA-gated and serotonin-gated chloride channels on C. elegans behavior. In the absence of KCC-2, chloride gradients appear to be altered in neurons and muscles such that normally inhibitory signals become excitatory. kcc-2 is transcriptionally upregulated in the HSN neurons during synapse development. Loss of KCC-2 produces a decrease in the synaptic vesicle population within mature HSN synapses, which apparently compensates for a lack of HSN inhibition, resulting in normal egg-laying behavior. Thus, KCC-2 coordinates the development of inhibitory neurotransmission with synapse maturation to produce mature neural circuits with appropriate activity levels.

Additional Information

Publication
Tannis, J., Bellemer, A., Moresco, J., Forbush, B., & Koelle, M. (2009). The Potassium Chloride Cotransporter KCC-2 Coordinates Development of Inhibitory Neurotransmission and Synapse Structure in Caenorhabditis elegans. Journal of Neuroscience, 29 (32). 9943-9954; DOI: https://doi.org/10.1523/JNEUROSCI.1989-09.2009. Publisher version of record available at: https://www.jneurosci.org/content/29/32/9943
Language: English
Date: 2009
Keywords
GABA, chloride, Caenorhabditis elegans

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