Physiological insight into the conserved properties of Caenorhabditis elegans acid-sensing degenerin/epithelia sodium channels

Acid -sensing ion channels (ASICs) are members of the diverse family of degenerin/epithelial sodium channels (DEG/ENaCs). hey 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 Caenorhabditis elegans DEG/ENaC family using two-electrode voltage clamp in Xenopus oocytes. We found two groups of acid-sensitive DEG/ENaCs characterised by being either 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 three 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 viva, as well as to study them as potential targets for anti-helminthic drugs.

Automated summary

Acid-sensing ion channels (ASICs) are important for physiological functions and disease. We discovered two acid-sensitive groups and identified seven acid-sensitive channels in the Caenorhabditis elegans DEG/ENaC family, three of which are functionally similar to vertebrate ASICs. These channels are expressed in both neurons and non-neuronal tissue, indicating functional diversity.