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

26 DEG/ENaC channels are voltage-independent Na or Na/Ca channels expressed in many 27 tissues and needed for a wide range of physiological functions, including sensory perception 28 and transepithelial Na transport. In the nervous system DEG/ENaCs are expressed both in 29 neurons and glia. However, the role of glial versus neuronal DEG/ENaCs remains unclear. We 30 recently reported the characterization of a novel DEG/ENaC in Caenorhabditis elegans that we 31 named ACD-1. ACD-1 is expressed in glial amphid sheath cells. The glial ACD-1 together with 32 the neuronal DEG/ENaC DEG-1 are necessary for acid avoidance and attraction to lysine. We 33 report here that knock-out of acd-1 in glia exacerbates sensory deficits caused by another 34 mutant: the hypomorphic allele of the cGMP-gated channel subunit tax-2. Furthermore, sensory 35 deficits caused by mutations in Gi protein odr-3 and guanylate cyclase daf-11, that regulate the 36 activity of TAX-2/TAX-4 channels, are worsened by knock-out of acd-1. We also show that 37 sensory neurons of acd-1 tax-2(p694) double mutants fail to undergo changes in intracellular 38 Ca when animals are exposed to low concentrations of attractant. Finally, we show that 39 exogenous expression of TRPV1 in sensory neurons and exposure to capsaicin rescue sensory 40 deficits of acd-1 tax-2(p694) mutants, suggesting that sensory deficits of these mutants are 41 bypassed by increasing neuronal excitability. Our data suggest a role of glial DEG/ENaC 42 channel ACD-1 in supporting neuronal activity. 43 44