{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:57:22Z","timestamp":1791518242279,"version":"4.3.4"},"reference-count":55,"publisher":"Wiley","issue":"2b","license":[{"start":{"date-parts":[[2011,8,28]],"date-time":"2011-08-28T00:00:00Z","timestamp":1314489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2011,9,2]]},"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND AND PURPOSE<\/jats:bold>\n                    Anthelmintics are required for treatment and prophylaxis of nematode parasites of humans and domestic animals. Emodepside, a cyclooctadepsipeptide, is a modern anthelmintic that has a novel mode of action involving a Ca\u2010activated K channel (SLO\u20101) in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , sometimes mediated by a latrophilin (LAT) receptor. We examined mechanisms of action of emodepside in a parasitic nematode,\n                    <jats:italic>Ascaris suum<\/jats:italic>\n                    .\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>\n                    RT\u2010PCR was used to investigate expression of\n                    <jats:italic>slo\u20101<\/jats:italic>\n                    and\n                    <jats:italic>lat\u20101<\/jats:italic>\n                    in\n                    <jats:italic>A. suum<\/jats:italic>\n                    muscle flaps, and two\u2010micropipette current\u2010clamp and voltage\u2010clamp techniques were used to record electrophysiological effects of emodepside.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>KEY RESULTS<\/jats:bold>\n                    Expression of\n                    <jats:italic>slo\u20101<\/jats:italic>\n                    and\n                    <jats:italic>lat\u20101<\/jats:italic>\n                    were detected. Emodepside produced a slow time\u2010dependent (20\u2003min), 4\u2010aminopyridine sensitive, concentration\u2010dependent hyperpolarization and increase in voltage\u2010activated K currents. Sodium nitroprusside increased the hyperpolarizations and K currents. N\u2010nitro\u2010L\u2010arginine inhibited the hyperpolarizations and K currents. Phorbol\u201012\u2010myristate\u201013 acetate increased the K currents, while staurosporine inhibited the hyperpolarizations and K currents. Iberiotoxin reduced these emodepside K currents. The effect of emodepside was reduced in Ca\u2010free solutions. Emodepside had no effect on voltage\u2010activated Ca currents.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold>\n                    <jats:italic>Asu\u2010slo\u20101<\/jats:italic>\n                    and\n                    <jats:italic>Asu\u2010lat\u20101<\/jats:italic>\n                    are expressed in adult\n                    <jats:italic>A. suum<\/jats:italic>\n                    muscle flaps and emodepside produces slow activation of voltage\u2010activated Ca\u2010dependent SLO\u20101\u2010like K channels. The effect of emodepside was enhanced by stimulation of protein kinase C and NO pathways. The data are consistent with a model in which NO, PKC and emodepside signalling pathways are separate and converge on the K channels, or in which emodepside activates NO and PKC signalling pathways to increase opening of the K channels.\n                  <\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01428.x","type":"journal-article","created":{"date-parts":[[2011,4,12]],"date-time":"2011-04-12T06:35:47Z","timestamp":1302590147000},"page":"453-470","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["On the mode of action of emodepside: slow effects on membrane potential and voltage\u2010activated currents in\n                    <i>Ascaris 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