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Therefore, strategies aimed at inhibiting Cav1.2 appear warranted. However, multiple clinical trials that attempted to treat bladder overactivity with calcium channel blockers (CCBs) have been unsuccessful, creating an unsolved mystery. In contrast, cardiologists and epidemiologists have reported strong associations between CCB use and bladder hyperactivity, opposing expectations of urologists. Recent findings from our lab offer a potential explanation. We have demonstrated that ketamine which can cause cystitis, functions, like nifedipine, as a Cav1.2 antagonist. We also show that a Cav1.2 agonist which potentiates muscle contraction, rather than antagonizing it, can increase the volume of voids and reduce voiding frequency. This perspective will discuss in detail the unsuccessful urological trials of CCBs and the promise of Cav1.2 agonists as potential novel therapies for bladder dysfunctions.<\/jats:p>","DOI":"10.1096\/fj.202101475r","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T16:52:32Z","timestamp":1640278352000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Reviving Cav1.2 as an attractive drug target to treat bladder dysfunction"],"prefix":"10.1096","volume":"36","author":[{"given":"Weiqun","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachuesetts 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