{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:28:58Z","timestamp":1774614538573,"version":"3.50.1"},"reference-count":119,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T00:00:00Z","timestamp":1666483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT103784MA"],"award-info":[{"award-number":["WT103784MA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Acid\u2010sensing 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\u00a0subunits of the\n                      <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                      DEG\/ENaC family using two\u2010electrode voltage clamp in\n                      <jats:italic>Xenopus<\/jats:italic>\n                      oocytes. We found two groups of acid\u2010sensitive DEG\/ENaCs characterised by being either inhibited or activated by increasing proton concentrations. Three of these acid\u2010sensitive\n                      <jats:italic>C. elegans<\/jats:italic>\n                      DEG\/ENaCs were activated by acidic pH, making them functionally similar to the vertebrate ASICs. We also identified three new members of the acid\u2010inhibited DEG\/ENaC group, giving a total of seven additional acid\u2010sensitive channels. We observed sensitivity to the anti\u2010hypertensive drug amiloride as well as modulation by the trace element zinc. Acid\u2010sensitive DEG\/ENaCs were found to be expressed in both neurons and non\u2010neuronal tissue, highlighting the likely functional diversity of these channels. Our findings provide a framework to exploit the\n                      <jats:italic>C. elegans<\/jats:italic>\n                      channels as models to study the function of these acid\u2010sensing channels\n                      <jats:italic>in vivo<\/jats:italic>\n                      , as well as to study them as potential targets for anti\u2010helminthic drugs.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15300-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Acidosis plays many roles in healthy physiology, including synaptic transmission and gut function, but is also a key feature of inflammatory pain, ischaemia and many other conditions. Cells monitor acidosis of their surroundings via pH\u2010sensing channels, including the acid\u2010sensing ion channels (ASICs). These are members of the degenerin\/epithelial sodium channel (DEG\/ENaC) family, along with, as the name suggests, vertebrate ENaCs and degenerins of the roundworm\n                            <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                            .\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            By screening all 30\n                            <jats:italic>C. elegans<\/jats:italic>\n                            DEG\/ENaCs for pH dependence, we describe, for the first time, three acid\u2010activated members, as well as three additional acid\u2010inhibited channels.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We surveyed both groups for sensitivity to amiloride and zinc; like their mammalian counterparts, their currents can be blocked, enhanced or unaffected by these modulators. Likewise, they exhibit diverse ion selectivity.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our findings underline the diversity of acid\u2010sensitive DEG\/ENaCs across species and provide a comparative resource for better understanding the molecular basis of their function.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp283238","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T05:29:57Z","timestamp":1665034197000},"page":"1625-1653","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Physiological insight into the conserved properties of\n                    <i>Caenorhabditis elegans<\/i>\n                    acid\u2010sensing degenerin\/epithelial sodium channels"],"prefix":"10.1113","volume":"601","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0868-3702","authenticated-orcid":false,"given":"Eva","family":"Kaulich","sequence":"first","affiliation":[{"name":"Neurobiology Division MRC Laboratory of Molecular Biology  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick T. 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