title: Knockout of glial channel ACD-1 exacerbates sensory deficits in a C. elegans mutant by regulating calcium levels of sensory neurons.
abstract: Degenerin/epithelial Na(+) channels (DEG/ENaCs) are voltage-independent Na(+) or Na(+)/Ca(2+) channels expressed in many tissues and are needed for a wide range of physiological functions, including sensory perception and transepithelial Na(+) transport. In the nervous system, DEG/ENaCs are expressed in both neurons and glia. However, the role of glial vs. neuronal DEG/ENaCs remains unclear. We recently reported the characterization of a novel DEG/ENaC in Caenorhabditis elegans that we named ACD-1. ACD-1 is expressed in glial amphid sheath cells. The glial ACD-1, together with the neuronal DEG/ENaC DEG-1, is necessary for acid avoidance and attraction to lysine. We report presently that knockout of acd-1 in glia exacerbates sensory deficits caused by another mutant: the hypomorphic allele of the cGMP-gated channel subunit tax-2. Furthermore, sensory deficits caused by mutations in G(i) protein odr-3 and guanylate cyclase daf-11, which regulate the activity of TAX-2/TAX-4 channels, are worsened by knockout of acd-1. We also show that sensory neurons of acd-1 tax-2(p694) double mutants fail to undergo changes in intracellular Ca(2+) when animals are exposed to low concentrations of attractant. Finally, we show that exogenous expression of TRPV1 in sensory neurons and exposure to capsaicin rescue sensory deficits of acd-1 tax-2(p694) mutants, suggesting that sensory deficits of these mutants are bypassed by increasing neuronal excitability. Our data suggest a role of glial DEG/ENaC channel ACD-1 in supporting neuronal activity.
authors: Rm. 5133, Rosenstiel Bldg., Dept. of Physiology and Biophysics, Miller School of Medicine, Univ. of Miami, 1600 NW 10th Ave., Miami, FL 33136, USA.
authors: Ying
authors: Y
authors: Wang
authors: Giulia
authors: G
authors: D'Urso
authors: Laura
authors: L
authors: Bianchi
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D015640:Ion Channel Gating; D009154:Mutation; D012678:Sensation Disorders / Q000503:physiopathology*
chemical_list: C532398:ACD-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D053503:Epithelial Sodium Channels; D002118:Calcium