{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T13:49:46Z","timestamp":1776001786835,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society of the Promotion of Sciences","award":["18H03182, 18K06643"],"award-info":[{"award-number":["18H03182, 18K06643"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In Ts1Rhr, a Down syndrome model mouse, the airway ciliary beatings are impaired; that is, decreases in ciliary beat frequency (CBF) and ciliary bend angle (CBA, an index of ciliary beat amplitude)). A resumption to two copies of the Pcp4 gene on the Ts1Rhr trisomic segment (Ts1Rhr:Pcp4+\/+\/-) rescues the decreases in CBF and CBA that occur in Ts1Rhr. In airway cilia, upon stimulation with procaterol (a \u03b22-agonist), the CBF increase is slower over the time course than the CBA increase because of cAMP degradation by Ca2+\/calmodulin-dependent phosphodiesterase 1 (PDE1) existing in the metabolon regulating CBF. In Ts1Rhr, procaterol-stimulated CBF increase was much slower over the time course than in the wild-type mouse (Wt) or Ts1Rhr:Pcp4+\/+\/-. However, in the presence of 8MmIBMX (8-methoxymethyl isobutylmethyl xanthine, an inhibitor of PDE1) or calmidazolium (an inhibitor of calmodulin), in both Wt and Ts1Rhr, procaterol stimulates CBF and CBA increases over a similar time course. Measurements of cAMP revealed that the cAMP contents were lower in Ts1Rhr than in Wt or in Ts1Rhr:Pcp4+\/+\/-, suggesting the activation of PDE1A that is present in Ts1Rhr airway cilia. Measurements of the intracellular Ca2+ concentration ([Ca2+]i) in airway ciliary cells revealed that temperature (increasing from 25 to 37 \u00b0C) or 4\u03b1PDD (a selective transient receptor potential vanilloid 4 (TRPV4) agonist) stimulates a larger [Ca2+]i increase in Ts1Rhr than in Wt or Ts1Rhr:Pcp4+\/+\/-. In airway ciliary cells of Ts1Rhr, Pcp4-dose dependent activation of TRPV4 appears to induce an increase in the basal [Ca2+]i. In early embryonic day mice, a basal [Ca2+]i increased by PCP4 expressed may affect axonemal regulatory complexes regulated by the Ca2+-signal in Ts1Rhr, leading to a decrease in the basal CBF and CBA of airway cilia.<\/jats:p>","DOI":"10.3390\/ijms21061947","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T12:22:51Z","timestamp":1584015771000},"page":"1947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Airway Ciliary Beating Affected by the Pcp4 Dose-Dependent [Ca2+]i Increase in Down Syndrome Mice, Ts1Rhr"],"prefix":"10.3390","volume":"21","author":[{"given":"Haruka","family":"Kogiso","sequence":"first","affiliation":[{"name":"Research Unit for Epithelial Physiology, Research Organization of Science and Technology, BKC, Ritsumeikan University, Kusatsu 525-8577, Japan"},{"name":"Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthieu","family":"Raveau","sequence":"additional","affiliation":[{"name":"Laboratory for Neurogenetics, RIKEN, Brain Science Institute, Saitama 351-0198, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Yamakawa","sequence":"additional","affiliation":[{"name":"Laboratory for Neurogenetics, RIKEN, Brain Science Institute, Saitama 351-0198, Japan"},{"name":"Department of Neurodevelopmental Disorder Genetics, Institute of Brain Sciences, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-cho, Mizuho-ku Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daichi","family":"Saito","sequence":"additional","affiliation":[{"name":"Research Unit for Epithelial Physiology, Research Organization of Science and Technology, BKC, Ritsumeikan University, Kusatsu 525-8577, Japan"},{"name":"Department of Molecular Physiology, Faculty of Pharmaceutical Sciences, BKC, Ritsumeikan University, Kusatsu 525-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Ikeuchi","sequence":"additional","affiliation":[{"name":"Research Unit for Epithelial Physiology, Research Organization of Science and Technology, BKC, Ritsumeikan University, Kusatsu 525-8577, Japan"},{"name":"Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomonori","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, Faculty of Pharmaceutical Sciences, BKC, Ritsumeikan University, Kusatsu 525-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Asano","sequence":"additional","affiliation":[{"name":"Research Unit for Epithelial Physiology, Research Organization of Science and Technology, BKC, Ritsumeikan University, Kusatsu 525-8577, Japan"},{"name":"Department of Molecular Physiology, Faculty of Pharmaceutical Sciences, BKC, Ritsumeikan University, Kusatsu 525-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshio","family":"Inui","sequence":"additional","affiliation":[{"name":"Research Unit for Epithelial Physiology, Research Organization of Science and Technology, BKC, Ritsumeikan University, Kusatsu 525-8577, Japan"},{"name":"Saisei Mirai Clinics, Moriguchi 570-0012, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3846-0937","authenticated-orcid":false,"given":"Yoshinori","family":"Marunaka","sequence":"additional","affiliation":[{"name":"Research Unit for Epithelial Physiology, Research Organization of Science and Technology, BKC, Ritsumeikan University, Kusatsu 525-8577, Japan"},{"name":"Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"},{"name":"Research Institute for Clinical Physiology, Kyoto Industrial Health Association, Kyoto 604-8472, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Nakahari","sequence":"additional","affiliation":[{"name":"Research Unit for Epithelial Physiology, Research Organization of Science and Technology, BKC, Ritsumeikan University, Kusatsu 525-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nrg1448","article-title":"Chromosome 21 and Down syndrome: From genomics to pathophysiology","volume":"5","author":"Antonarakis","year":"2004","journal-title":"Nat. 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