{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T10:59:36Z","timestamp":1764586776439},"reference-count":22,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,9,4]],"date-time":"2012-09-04T00:00:00Z","timestamp":1346716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background\u2002<\/jats:bold> Studies on animal models of Hirschsprung\u2019s disease (HD) suggest that L\u2010type Ca<jats:sup>2+<\/jats:sup> channels are down\u2010regulated in the aganglionic bowel segment, however, this has yet to be confirmed in HD patients. The objective of this study was to test the hypothesis that L\u2010type Ca<jats:sup>2+<\/jats:sup> current density is decreased in smooth muscle cells (SMC) obtained from the aganglionic bowel segment of patients with HD in comparison with those from the ganglionic segment.<\/jats:p><jats:p><jats:bold>Methods\u2002<\/jats:bold> Smooth muscle cells were freshly isolated from colon samples obtained from HD patients undergoing pull\u2010through surgery. L\u2010type Ca<jats:sup>2+<\/jats:sup> currents were recorded using the perforated patch configuration of the whole cell voltage clamp technique and the expression levels of CACNA1C transcripts (which encode L\u2010type Ca<jats:sup>2+<\/jats:sup> channels) in the ganglionic and aganglionic bowel segments were compared using real\u2010time quantitative PCR.<\/jats:p><jats:p><jats:bold>Key Results\u2002<\/jats:bold> All SMC displayed robust currents that had activation\/inactivation kinetics typical of L\u2010type Ca<jats:sup>2+<\/jats:sup> current, were inhibited by nifedipine and enhanced by the L\u2010type Ca<jats:sup>2+<\/jats:sup> channel agonists FPL 64176 and Bay K 8644. Moreover, FPL 64176 activated currents were also inhibited by nifedipine. However, there was no significant difference in L\u2010type Ca<jats:sup>2+<\/jats:sup> current density, CACNA1C subunit expression or sensitivity to the pharmacological agents noted above, between SMC isolated from the ganglionic and aganglionic regions of the HD colon.<\/jats:p><jats:p><jats:bold>Conclusions &amp; Inferences\u2002<\/jats:bold> In contrast to studies on genetic animal models of HD, L\u2010type Ca<jats:sup>2+<\/jats:sup> currents are not down\u2010regulated in the aganglionic bowel segment of HD patients and are therefore unlikely to account for the impaired colonic peristalsis observed in these patients.<\/jats:p>","DOI":"10.1111\/nmo.12006","type":"journal-article","created":{"date-parts":[[2012,9,5]],"date-time":"2012-09-05T02:23:25Z","timestamp":1346811805000},"page":"1126","source":"Crossref","is-referenced-by-count":3,"title":["Investigation of L\u2010type Ca<sup>2+<\/sup> current in the aganglionic bowel segment in Hirschsprung\u2019s disease"],"prefix":"10.1111","volume":"24","author":[{"given":"R. J.","family":"Large","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Bradley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Webb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. M.","family":"O\u2019Donnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Puri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. A.","family":"Hollywood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. D.","family":"Thornbury","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. G.","family":"McHale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. P.","family":"Sergeant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,9,4]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2008.01256.x"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1067\/msy.2002.119963"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00352.2006"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019304"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.018986"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.61.1.85"},{"key":"e_1_2_8_8_2","first-page":"347","article-title":"Responses of narrow segments of intestines in the congenital aganglionosis rat to various stimulants","volume":"18","author":"Ikadai H","year":"1982","journal-title":"Nihon HeikatsukinGakkaiZasshi"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2007.05.020"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(91)90017-T"},{"key":"e_1_2_8_11_2","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1152\/physrev.1994.74.2.365","article-title":"Regulation and modulation of calcium channels in cardiac, skeletal and smooth muscle cells","volume":"742","author":"McDonald TF","year":"1994","journal-title":"Physiol Rev"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00071a004"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-9254-3_2"},{"issue":"3","key":"e_1_2_8_14_2","doi-asserted-by":"crossref","first-page":"C451","DOI":"10.1152\/ajpcell.1989.257.3.C451","article-title":"Participation of Ca currents in colonic electrical activity","volume":"257","author":"Langton PD","year":"1989","journal-title":"Am J Physiol"},{"issue":"3","key":"e_1_2_8_15_2","doi-asserted-by":"crossref","first-page":"C745","DOI":"10.1152\/ajpcell.1993.264.3.C745","article-title":"Dihydropyridine\u2010sensitive calcium channels expressed in canine colonic smooth muscle cells","volume":"264","author":"Rich A","year":"1993","journal-title":"Am J Physiol"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02584005"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1990.sp017901"},{"issue":"3","key":"e_1_2_8_18_2","first-page":"G378","article-title":"Ca2+ currents in human colonic smooth muscle cells","volume":"269","author":"Xiong Z","year":"1995","journal-title":"Am J Physiol"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00038.2003"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.21167"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.50.3.355"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.11.729"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21211"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnmo.12006","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.12006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T22:20:54Z","timestamp":1698704454000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.12006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,4]]},"references-count":22,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["10.1111\/nmo.12006"],"URL":"https:\/\/doi.org\/10.1111\/nmo.12006","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,4]]}}}