{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T02:59:42Z","timestamp":1764212382083,"version":"3.44.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG058814, DK120824"],"award-info":[{"award-number":["AG058814, DK120824"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031147","name":"Duke Claude D. Pepper Older Americans Independence Center, Duke Aging Center, Duke University","doi-asserted-by":"publisher","award":["P30 AG067988"],"award-info":[{"award-number":["P30 AG067988"]}],"id":[{"id":"10.13039\/100031147","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["LUTS"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to investigate the potential role of cesium chloride (CsCl), ivabradine (IVA), and isoproterenol (ISO) on the sensory transmission of bladder afferents to graded urinary bladder distension (UBD). We specifically selected these drugs to target the hyperpolarization\u2010activated cyclic nucleotide\u2010gated (HCN) cation channels to determine their role in afferent encoding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The bladders of C57BL\/6 female mice were harvested with attached pelvic nerves in continuity, and the stimulus\u2013response function (SRF) of bladder afferents to stepped bladder distension (20, 40, 60, 80\u2009cmH<jats:sub>2<\/jats:sub>O) was recorded by single\u2010fiber recordings. Their changes in SRF to bath application of CsCl, IVA, and ISO were then evaluated. The presence of HCN on bladder afferent endings was assessed through immunohistological staining on bladder sections from mice with genetically labeled bladder afferents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IVA and ISO did not significantly reduce afferent responses to UBD, whereas CsCl increased afferent responses. Bladder afferents in the pelvic nerve pathway were categorized into low\u2010firing (LF, &lt;\u200910\u2009Hz) and high\u2010firing (HF, &gt;\u200910\u2009Hz) groups. SRF in both the LF and HF groups showed similar trends with no significant changes in response to IVA and ISO. CsCl increased SRF only in the HF group but not in the LF group. Immunohistological staining revealed that HCN1 does not extensively co\u2010localize with afferent endings, showing only sporadic presence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our targeted pharmacological studies with single\u2010fiber recordings and immunohistological staining collectively suggest that HCN channels do not play a significant role in bladder afferent sensory transmission.<\/jats:p><\/jats:sec>","DOI":"10.1111\/luts.70025","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T08:31:19Z","timestamp":1754382679000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacological Targeting of Hyperpolarization\u2010Activated Cyclic Nucleotide\u2010Gated Cation Channels on Bladder Afferent Sensory Transmission"],"prefix":"10.1111","volume":"17","author":[{"given":"Eric","family":"Woon","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Connecticut  Storrs Connecticut USA"},{"name":"UConn Center on Aging UConn Health  Farmington Connecticut USA"},{"name":"Department of Surgery University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge Villalobos","family":"Santeli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Connecticut  Storrs Connecticut USA"},{"name":"Department of Physiology and Neurobiology University of Connecticut  Storrs Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Connecticut  Storrs Connecticut USA"},{"name":"Department of Engineering and Aviation Sciences University of Maryland Eastern Shore  Princess Anne Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longtu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Connecticut  Storrs Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8387-7040","authenticated-orcid":false,"given":"George","family":"Kuchel","sequence":"additional","affiliation":[{"name":"UConn Center on Aging UConn Health  Farmington Connecticut USA"},{"name":"Department of Surgery University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9277-211X","authenticated-orcid":false,"given":"Bin","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Connecticut  Storrs Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.24958"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2010.09993.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2011.03.132"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4161\/org.25895"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2016.11.006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)36981-1"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.24149"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13990"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)36619-3"},{"key":"e_1_2_9_11_1","first-page":"S3","article-title":"The Aging Bladder","volume":"6","author":"Siroky M. 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