{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T21:21:35Z","timestamp":1782940895084,"version":"3.54.5"},"reference-count":53,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T00:00:00Z","timestamp":1553731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["1\u00a0SD\u00a0RR16871"],"award-info":[{"award-number":["1\u00a0SD\u00a0RR16871"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK57236"],"award-info":[{"award-number":["DK57236"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK41315"],"award-info":[{"award-number":["DK41315"]}],"id":[{"id":"10.13039\/100000062","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":[[2019,5]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Electrical pacemaking in gastrointestinal muscles is generated by specialized interstitial cells of Cajal that produce the patterns of contractions required for peristalsis and segmentation in the gut.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The calcium\u2010activated chloride conductance anoctamin\u20101 (Ano1) has been shown to be responsible for the generation of pacemaker activity in GI muscles, but this conclusion is established from studies of juvenile animals in which effects of reduced Ano1 on gastric emptying and motor patterns could not be evaluated.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Knocking down Ano1 expression using Cre\/LoxP technology caused dramatic changes in in gastric motor activity, with disrupted slow waves, abnormal phasic contractions and delayed gastric emptying; modest changes were noted in the small intestine.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Comparison of the effects of Ano1 antagonists on muscles from juvenile and adult small intestinal muscles suggests that conductances in addition to Ano1 may develop with age and contribute to pacemaker activity.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Interstitial cells of Cajal (ICC) generate slow waves and transduce neurotransmitter signals in the gastrointestinal (GI) tract, facilitating normal motility patterns. ICC express a Ca<jats:sup>2+<\/jats:sup>\u2010activated Cl<jats:italic><jats:sup>\u2212<\/jats:sup><\/jats:italic> conductance (CaCC), and constitutive knockout of the channel protein anoctamin\u20101 leads to loss of slow waves in gastric and intestinal muscles. These knockout experiments were performed on juvenile mice. However, additional experiments demonstrated significant differences in the sensitivity of gastric and intestinal muscles to antagonists of anoctamin\u20101 channels. Furthermore, the significance of anoctamin\u20101 and the electrical and mechanical behaviours facilitated by this conductance have not been evaluated on the motor behaviours of adult animals. Cre\/loxP technology was used to generate cell\u2010specific knockdowns of anoctamin\u20101 in ICC (<jats:italic>Kit<jats:sup>CreERT2\/+<\/jats:sup>;Ano1<jats:sup>tm2jrr\/+<\/jats:sup><\/jats:italic>) in GI muscles. The recombination efficiency of <jats:italic>Kit<jats:sup>CreERT<\/jats:sup><\/jats:italic> was evaluated with an eGFP reporter, molecular techniques and immunohistochemistry. Electrical and contractile experiments were used to examine the consequences of anoctamin\u20101 knockdown on pacemaker activity, mechanical responses, gastric motility patterns, gastric emptying and GI transit. Reduced anoctamin\u20101 caused loss of gastric, but not intestinal slow waves. Irregular spike complexes developed in gastric muscles, leading to uncoordinated antral contractions, delayed gastric emptying and increased total GI transit time. Slow waves in intestinal muscles of juvenile mice were more sensitive to anoctamin\u20101 antagonists than slow waves in adult muscles. The low susceptibility to anoctamin\u20101 knockdown and weak efficacy of anoctamin\u20101 antagonists in inhibiting slow waves in adult small intestinal muscles suggest that a conductance in addition to anoctamin\u20101 may develop in small intestinal ICC with ageing and contribute to pacemaker activity.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp277335","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T09:46:01Z","timestamp":1551951961000},"page":"2337-2360","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Differential sensitivity of gastric and small intestinal muscles to inducible knockdown of anoctamin 1 and the effects on gastrointestinal motility"],"prefix":"10.1113","volume":"597","author":[{"given":"Sung Jin","family":"Hwang","sequence":"first","affiliation":[{"name":"Department of Physiology &amp; Cell Biology University of Nevada Reno School of Medicine  Reno NV 89557 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Pardo","sequence":"additional","affiliation":[{"name":"Department of Anatomy University of California  San Francisco San Francisco CA 94143 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology University of Nevada Reno School of Medicine  Reno NV 89557 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Bayguinov","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology University of Nevada Reno School of Medicine  Reno NV 89557 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Blair","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology University of Nevada Reno School of Medicine  Reno NV 89557 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Fortune\u2010Grant","sequence":"additional","affiliation":[{"name":"Faculty of Biology Medicine and Health School of Biological Sciences University of Manchester  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Cook","sequence":"additional","affiliation":[{"name":"School of Molecular and Cellular Biology University of Leeds  Leeds LS2 9JT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant W.","family":"Hennig","sequence":"additional","affiliation":[{"name":"Department of Pharmacology The University of Vermont UVM College of Medicine  Burlington VT 05405 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C.","family":"Shonnard","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology University of Nevada Reno School of Medicine  Reno NV 89557 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Grainger","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology University of Nevada Reno School of Medicine  Reno NV 89557 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Peri","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology University of Nevada Reno School of Medicine  Reno NV 89557 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonali Deep","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Anatomy University of California  San Francisco San Francisco CA 94143 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Rock","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine Boston University School of Medicine  Boston MA 02118 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4196-1583","authenticated-orcid":false,"given":"Kenton M.","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology University of Nevada Reno School of Medicine  Reno NV 89557 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0217-1535","authenticated-orcid":false,"given":"Sean M.","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Cell Biology University of Nevada Reno School of Medicine  Reno NV 89557 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.96"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-012-1468-7"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm14060"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8529(05)70328-5"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.06.018"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00113.2007"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000496041"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273618"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00548.2006"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201711771"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.535"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2014.11.004"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00074.2009"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.063875"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.01.038"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.01.046"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270818"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.0575t.x"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.014803"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/373347a0"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13431"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.176198"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-002-0884-z"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.051334"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2626"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.203by.x"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.04.018"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176031"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00363.2016"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.196089"},{"key":"e_1_2_5_32_1","first-page":"211","article-title":"Accurate measurement of intestinal transit in the rat","volume":"6","author":"Miller MS","year":"1981","journal-title":"J\u00a0Pharmacol Methods 1981"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12806"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.06.009"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v111.pm8690216"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.168"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00037.2013"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1559-2"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00062.2016"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.277152"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00196.2011"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00429.2016"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP275478"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00070.2016"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.0563t.x"},{"key":"e_1_2_5_47_1","first-page":"97","article-title":"c\u2010kit\u2010dependent development of interstitial cells and electrical activity in the murine gastrointestinal tract","volume":"280","author":"Torihashi S","year":"1995","journal-title":"Cell Tissue Res"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.269.6.C1577"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020343"},{"key":"e_1_2_5_50_1","first-page":"741","article-title":"Gastroparesis: current management","volume":"21","author":"Webb WW","year":"1995","journal-title":"Compr Ther"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07313"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00390.2013"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.176206"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00360.2014"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP277335","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP277335","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP277335","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP277335","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T02:42:41Z","timestamp":1694227361000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP277335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,28]]},"references-count":53,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1113\/JP277335"],"URL":"https:\/\/doi.org\/10.1113\/jp277335","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,28]]},"assertion":[{"value":"2018-10-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}