@article {Branicky764, author = {Robyn Branicky and Hiroaki Miyazaki and Kevin Strange and William R. Schafer}, title = {The Voltage-Gated Anion Channels Encoded by clh-3 Regulate Egg Laying in C. elegans by Modulating Motor Neuron Excitability}, volume = {34}, number = {3}, pages = {764--775}, year = {2014}, doi = {10.1523/JNEUROSCI.3112-13.2014}, publisher = {Society for Neuroscience}, abstract = {CLC-2 is a hyperpolarization-activated, inwardly rectifying chloride channel. Although the properties of the CLC-2 channel have been well characterized, its function in vivo is not well understood. We have found that channels encoded by the Caenorhabditis elegans CLC-2 homolog clh-3 regulate the activity of the spontaneously active hermaphrodite-specific neurons (HSNs), which control the egg-laying behavior. We identified a gain-of-function mutation in clh-3 that increases channel activity. This mutation inhibits egg laying and inhibits HSN activity by decreasing its excitability. Conversely, loss-of-function mutations in clh-3 lead to misregulated egg laying and an increase in HSN excitability, indicating that these channels modulate egg laying by limiting HSN excitability. clh-3-encoded channels are not required for GABAA-receptor-mediated inhibition of the HSN. However, they require low intracellular chloride for HSN inhibition, indicating that they inhibit excitability directly by mediating chloride influx. This mechanism of CLH-3-dependent modulation may be conserved in other neurons in which the driving force favors chloride influx.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/34/3/764}, eprint = {https://www.jneurosci.org/content/34/3/764.full.pdf}, journal = {Journal of Neuroscience} }