PT  - JOURNAL ARTICLE
AU  - Eva Kaulich
AU  - Patrick T. N. McCubbin
AU  - William R. Schafer
AU  - Denise S. Walker
TI  - Physiological insight into the conserved properties of <em>Caenorhabditis elegans</em> acid-sensing DEG/ENaCs
AID  - 10.1101/2022.04.12.488049
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.04.12.488049
4099  - http://biorxiv.org/content/early/2022/04/13/2022.04.12.488049.short
4100  - http://biorxiv.org/content/early/2022/04/13/2022.04.12.488049.full
AB  - Acid sensing ion channels (ASICs) are members of the diverse family of degenerin/epithelial sodium channels (DEG/ENaCs). They perform a wide range of physiological roles in healthy organisms, including in gut function and synaptic transmission, but also play important roles in disease, as acidosis is a hallmark of painful inflammatory and ischaemic conditions. We performed a screen for acid-sensitivity on all 30 subunits of the C. elegans DEG/ENaC family using Two-Electrode Voltage Clamp (TEVC) in Xenopus oocytes. We found two groups of acid-sensing DEG/ENaCs characterised by being inhibited or activated by increasing proton concentrations. Three of these acid-sensitive C. elegans DEG/ENaCs were activated by acidic pH, making them functionally similar to the vertebrate ASICs. We also identified four new members of the acid-inhibited DEG/ENaC group, giving a total of seven additional acid-sensitive channels. We observed sensitivity to the anti-hypertensive drug amiloride as well as modulation by the trace element zinc. Acid-sensitive DEG/ENaCs were found to be expressed in both neurons and non-neuronal tissue, highlighting the likely functional diversity of these channels. Our findings provide a framework to exploit the C. elegans channels as models to study the function of these acid-sensing channels in vivo, as well as to study them as potential targets for anti-helminthic drugs.Competing Interest StatementThe authors have declared no competing interest.