2026-06-28T20:30:32Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/1346622026-04-14T00:19:50Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Herrera, Gerald M author Rengo, Jason L author Hennig, Grant W author Heppner, Thomas J author Hepp, Alexandria M author Sancho González, María author Huerta de la Cruz, Saul author Nelson, Mark T author Klug, Nicholas R 2026-04-13T08:09:55Z 2026-04-13T08:09:55Z 2026 Herrera GM, Rengo JL, Hennig GW, Heppner TJ, Hepp AM, Sancho M, Huerta de la Cruz S, Nelson MT, Klug NR. Adenosine and acute low oxygen conditions suppress urinary bladder contractility through the activation of adenosine 2B receptors and large-conductance calcium-activated potassium channels. J Physiol. 2026 Jan;604(1):379-394. doi: 10.1113/JP289080. 1469-7793 10.1113/JP289080 https://hdl.handle.net/20.500.14352/134662 https://doi.org/10.1113/JP289080 41160530 https://physoc.onlinelibrary.wiley.com/journal/14697793 Under healthy conditions the urinary bladder undergoes relatively long periods of filling with well-spaced 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-voiding 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-voiding 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 ex vivo pressurized bladder preparation from mice and patch-clamp electrophysiology in isolated UBSM cells, we evaluated whole bladder transient pressure events, whole bladder detrusor Ca 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-conductance calcium-activated potassium (BK) 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. KEY POINTS: This study shows that adenosine, a signalling molecule, reduces bladder contractility by activating A2B receptors and large-conductance calcium-activated potassium (BK) channels. Low oxygen conditions also suppress bladder activity through the activation of A2B receptors, linking acute hypoxia to bladder relaxation. ATP-sensitive potassium (K) channels, often involved in muscle relaxation, do not contribute to adenosine's effects in the bladder. 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. eng Adenosine and acute low oxygen conditions suppress urinary bladder contractility through the activation of adenosine 2B receptors and large-conductance calcium-activated potassium channels. journal article 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URL https://docta.ucm.es/bitstreams/fedca030-88e9-497a-96c7-58564ece144c/download File MD5 fae280f9da07318f8605f5fbb7a9c1bc 2661190 application/pdf Adenosine and acute low oxygen conditions supress urinary bladder contractility.pdf