Knockout of glial channel ACD-1 exacerbates sensory deficits in a C. elegans mutant by regulating calcium levels of sensory neurons.

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.