Urothelium-Specific Deletion of Connexin43 in the Mouse Urinary Bladder Alters Distension-Induced ATP Release and Voiding Behavior
Connexin43 (Cx43), the main gap junction and hemichannel forming protein in the urinary bladder, participates in the regulation of bladder motor and sensory functions and has been reported as an important modulator of day–night variations in functional bladder capacity. However, because Cx43 is expr...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/1594 |
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| author | Jin Kono Masakatsu Ueda Atsushi Sengiku Sylvia O. Suadicani Osamu Ogawa Hiromitsu Negoro |
| author_facet | Jin Kono Masakatsu Ueda Atsushi Sengiku Sylvia O. Suadicani Osamu Ogawa Hiromitsu Negoro |
| author_sort | Jin Kono |
| collection | DOAJ |
| description | Connexin43 (Cx43), the main gap junction and hemichannel forming protein in the urinary bladder, participates in the regulation of bladder motor and sensory functions and has been reported as an important modulator of day–night variations in functional bladder capacity. However, because Cx43 is expressed throughout the bladder, the actual role played by the detrusor and the urothelial Cx43 is still unknown. For this purpose, we generated urothelium-specific Cx43 knockout (uCx43KO) mice using Cre-LoxP system. We evaluated the day–night micturition pattern and the urothelial Cx43 hemichannel function of the uCx43KO mice by measuring luminal ATP release after bladder distention. In wild-type (WT) mice, distention-induced ATP release was elevated, and functional bladder capacity was decreased in the animals’ active phase (nighttime) when Cx43 expression was also high compared to levels measured in the sleep phase (daytime). These day–night differences in urothelial ATP release and functional bladder capacity were attenuated in uCx43KO mice that, in the active phase, displayed lower ATP release and higher functional bladder capacity than WT mice. These findings indicate that urothelial Cx43 mediated ATP signaling and coordination of urothelial activity are essential for proper perception and regulation of responses to bladder distension in the animals’ awake, active phase. |
| first_indexed | 2024-03-09T05:37:27Z |
| format | Article |
| id | doaj.art-1dad84d35c0946e5b60996bd590b7d77 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:37:27Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1dad84d35c0946e5b60996bd590b7d772023-12-03T12:27:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224159410.3390/ijms22041594Urothelium-Specific Deletion of Connexin43 in the Mouse Urinary Bladder Alters Distension-Induced ATP Release and Voiding BehaviorJin Kono0Masakatsu Ueda1Atsushi Sengiku2Sylvia O. Suadicani3Osamu Ogawa4Hiromitsu Negoro5Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, JapanDepartment of Urology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, JapanDepartment of Urology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, JapanDepartment of Urology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Urology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, JapanDepartment of Urology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, JapanConnexin43 (Cx43), the main gap junction and hemichannel forming protein in the urinary bladder, participates in the regulation of bladder motor and sensory functions and has been reported as an important modulator of day–night variations in functional bladder capacity. However, because Cx43 is expressed throughout the bladder, the actual role played by the detrusor and the urothelial Cx43 is still unknown. For this purpose, we generated urothelium-specific Cx43 knockout (uCx43KO) mice using Cre-LoxP system. We evaluated the day–night micturition pattern and the urothelial Cx43 hemichannel function of the uCx43KO mice by measuring luminal ATP release after bladder distention. In wild-type (WT) mice, distention-induced ATP release was elevated, and functional bladder capacity was decreased in the animals’ active phase (nighttime) when Cx43 expression was also high compared to levels measured in the sleep phase (daytime). These day–night differences in urothelial ATP release and functional bladder capacity were attenuated in uCx43KO mice that, in the active phase, displayed lower ATP release and higher functional bladder capacity than WT mice. These findings indicate that urothelial Cx43 mediated ATP signaling and coordination of urothelial activity are essential for proper perception and regulation of responses to bladder distension in the animals’ awake, active phase.https://www.mdpi.com/1422-0067/22/4/1594urotheliumconnexin43gap junctionhemichannelATP |
| spellingShingle | Jin Kono Masakatsu Ueda Atsushi Sengiku Sylvia O. Suadicani Osamu Ogawa Hiromitsu Negoro Urothelium-Specific Deletion of Connexin43 in the Mouse Urinary Bladder Alters Distension-Induced ATP Release and Voiding Behavior International Journal of Molecular Sciences urothelium connexin43 gap junction hemichannel ATP |
| title | Urothelium-Specific Deletion of Connexin43 in the Mouse Urinary Bladder Alters Distension-Induced ATP Release and Voiding Behavior |
| title_full | Urothelium-Specific Deletion of Connexin43 in the Mouse Urinary Bladder Alters Distension-Induced ATP Release and Voiding Behavior |
| title_fullStr | Urothelium-Specific Deletion of Connexin43 in the Mouse Urinary Bladder Alters Distension-Induced ATP Release and Voiding Behavior |
| title_full_unstemmed | Urothelium-Specific Deletion of Connexin43 in the Mouse Urinary Bladder Alters Distension-Induced ATP Release and Voiding Behavior |
| title_short | Urothelium-Specific Deletion of Connexin43 in the Mouse Urinary Bladder Alters Distension-Induced ATP Release and Voiding Behavior |
| title_sort | urothelium specific deletion of connexin43 in the mouse urinary bladder alters distension induced atp release and voiding behavior |
| topic | urothelium connexin43 gap junction hemichannel ATP |
| url | https://www.mdpi.com/1422-0067/22/4/1594 |
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