{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T19:11:31Z","timestamp":1786821091047,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK125543"],"award-info":[{"award-number":["R01DK125543"]}],"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":["F99DK143563"],"award-info":[{"award-number":["F99DK143563"]}],"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":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Under healthy conditions the urinary bladder undergoes relatively long periods of filling with well\u2010spaced voiding events to ensure proper storage and removal of urine. During the filling phase distinct contractile events in the urinary bladder smooth muscle (UBSM) comprising the detrusor elicit transient non\u2010voiding pressure events and associated bursts in afferent nerve activity to relay the sensation of bladder fullness. The mechanisms that regulate UBSM excitability and associated non\u2010voiding pressure events under physiological and pathological conditions are poorly understood. Here we investigated the role of adenosine signalling in regulating urinary bladder contractility. Using an\n                      <jats:italic>ex vivo<\/jats:italic>\n                      pressurized bladder preparation from mice and patch\u2010clamp electrophysiology in isolated UBSM cells, we evaluated whole bladder transient pressure events, whole bladder detrusor Ca\n                      <jats:sup>2+<\/jats:sup>\n                      activity and single UBSM ion channel activity. We found that adenosine suppresses bladder activity through the activation of A2B adenosine receptors and downstream activation of large\u2010conductance calcium\u2010activated potassium (BK\n                      <jats:sub>Ca<\/jats:sub>\n                      ) channels. We further demonstrated that acute exposure to low oxygen conditions using a chemical oxygen scavenger potently suppresses bladder contractility through the A2B receptor pathway. These results highlight the prominent role adenosine receptors and downstream potassium channels play in regulating urinary bladder contractility in physiological and pathological contexts.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70182-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            This study shows that adenosine, a signalling molecule, reduces bladder contractility by activating A2B receptors and large\u2010conductance calcium\u2010activated potassium (BK\n                            <jats:sub>Ca<\/jats:sub>\n                            ) channels.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Low oxygen conditions also suppress bladder activity through the activation of A2B receptors, linking acute hypoxia to bladder relaxation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            ATP\u2010sensitive potassium (K\n                            <jats:sub>ATP<\/jats:sub>\n                            ) channels, often involved in muscle relaxation, do not contribute to adenosine's effects in the bladder.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These findings reveal a new pathway that controls bladder function and may help explain bladder disorders related to low oxygen, such as overactive or underactive bladder.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp289080","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:54:23Z","timestamp":1761764063000},"page":"379-394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Adenosine and acute low oxygen conditions suppress urinary bladder contractility through the activation of adenosine 2B receptors and large\u2010conductance calcium\u2010activated potassium channels"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9029-0093","authenticated-orcid":false,"given":"Gerald M.","family":"Herrera","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Larner College of Medicine University of Vermont  Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0232-8339","authenticated-orcid":false,"given":"Jason L.","family":"Rengo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Larner College of Medicine University of Vermont  Burlington Vermont USA"},{"name":"Cellular, Molecular, and Biomedical Sciences Graduate Program University of Vermont  Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7436-9458","authenticated-orcid":false,"given":"Grant W.","family":"Hennig","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Larner College of Medicine University of Vermont  Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8052-7192","authenticated-orcid":false,"given":"Thomas J.","family":"Heppner","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Larner College of Medicine University of Vermont  Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandria M.","family":"Hepp","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Larner College of Medicine University of Vermont  Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4750-1040","authenticated-orcid":false,"given":"Maria","family":"Sancho","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Larner College of Medicine University of Vermont  Burlington Vermont USA"},{"name":"Department of 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