{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T04:33:51Z","timestamp":1719203631242},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T00:00:00Z","timestamp":1363046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"William E. Bradley Family Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>We investigated the mechanisms of diabetic bladder dysfunction (BD) through analysis of the roles of L\u2010 and T\u2010type voltage\u2010gated calcium channels (VGCCs), with the ultimate goal of identifying potential drug targets for diabetic BD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bladder function of <jats:italic>db\/db<\/jats:italic> (type 2 diabetes) and wild type (<jats:italic>Wt<\/jats:italic>) mice was evaluated by behavioral tests and in vivo cystometry. Contractile responses of bladder strips to carbachol were measured with or without pre\u2010treatment with nifedipine (a L\u2010type VGCC blocker) or mibefradil (a T\u2010type VGCC blocker). Furthermore, the effects of mibefradil and nifedipine on the proliferation of human bladder smooth muscle cells (BSMCs) were studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>db\/db<\/jats:italic> mice had significantly increased voiding frequency, bladder weight, bladder compliance and capacity, and heightened contractile response to carbachol, compared to <jats:italic>Wt<\/jats:italic> mice. Nifedipine, but not mibefradil, dramatically suppressed bladder tissue contraction in <jats:italic>Wt<\/jats:italic> mice. Whereas nifedipine nearly completely inhibited bladder contraction in <jats:italic>db\/db<\/jats:italic> mice, mibefradil \u201cnormalized\u201d the heightened bladder contractility of <jats:italic>db\/db<\/jats:italic> mice to the level of <jats:italic>Wt<\/jats:italic> mice. In culture, mibefradil, but not nifedipine, inhibited the proliferation of human BSMCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate that while L\u2010type VGCCs play a major role in the contraction of both diabetic and non\u2010diabetic bladders, T\u2010type VGCCs are involved in the contraction of diabetic bladders and mediate BSMC proliferation. This study provides support for further investigations on the effect of blockade of T\u2010type VGCC or combined blockade of both types of VGCCs in the treatment of diabetic BD. <jats:italic>Neurourol. Urodynam. 33:147\u2013152, 2014<\/jats:italic>. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.22391","type":"journal-article","created":{"date-parts":[[2013,3,14]],"date-time":"2013-03-14T03:30:06Z","timestamp":1363231806000},"page":"147-152","source":"Crossref","is-referenced-by-count":12,"title":["T\u2010 and L\u2010Type Voltage\u2010Gated Calcium Channels: Their Role in Diabetic Bladder Dysfunction"],"prefix":"10.1002","volume":"33","author":[{"given":"Xiaogang","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Urology University of Washington Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Luttrell","sequence":"additional","affiliation":[{"name":"Department of Urology University of Washington Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanchan","family":"Chitaley","sequence":"additional","affiliation":[{"name":"Department of Urology University of Washington Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire C.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology University of Washington Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,12]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"Centers for Disease Control and Prevention.National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States 2011. 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