title: The voltage-gated anion channels encoded by clh-3 regulate egg laying in C. elegans by modulating motor neuron excitability.
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.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, United Kingdom, and Boylan Center for Cellular and Molecular Physiology, Mount Desert Island Biological Laboratory, Salisbury Cove, Maine 04672.
authors.forename: Robyn
authors.initials: R
authors.lastname: Branicky
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Kevin
authors.initials: K
authors.lastname: Strange
authors.forename: William R
authors.initials: WR
authors.lastname: Schafer
mesh_terms: D000818:Animals; D000090007:CLC-2 Chloride Channels; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D009046:Motor Neurons / Q000502:physiology*; D010058:Oviposition / Q000502:physiology*
chemical_list: D000090007:CLC-2 Chloride Channels; D029742:Caenorhabditis elegans Proteins; D018118:Chloride Channels; C417201:clh-3 protein, C elegans