{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T18:04:27Z","timestamp":1718647467681},"reference-count":38,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2012,6,1]]},"abstract":"<jats:p> The functional role of the voltage-gated K<jats:sup>+<\/jats:sup> (K<jats:sub>V<\/jats:sub>) channels in human detrusor smooth muscle (DSM) is largely unexplored. Here, we provide molecular, electrophysiological, and functional evidence for the expression of K<jats:sub>V<\/jats:sub>2.1, K<jats:sub>V<\/jats:sub>2.2, and the electrically silent K<jats:sub>V<\/jats:sub>9.3 subunits in human DSM. Stromatoxin-1 (ScTx1), a selective inhibitor of K<jats:sub>V<\/jats:sub>2.1, K<jats:sub>V<\/jats:sub>2.2, and K<jats:sub>V<\/jats:sub>4.2 homotetrameric channels and of K<jats:sub>V<\/jats:sub>2.1\/9.3 heterotetrameric channels, was used to examine the role of these channels in human DSM function. Human DSM tissues were obtained during open bladder surgeries from patients without a history of overactive bladder. Freshly isolated human DSM cells were studied using RT-PCR, immunocytochemistry, live-cell Ca<jats:sup>2+<\/jats:sup> imaging, and the perforated whole cell patch-clamp technique. Isometric DSM tension recordings of human DSM isolated strips were conducted using tissue baths. RT-PCR experiments showed mRNA expression of K<jats:sub>V<\/jats:sub>2.1, K<jats:sub>V<\/jats:sub>2.2, and K<jats:sub>V<\/jats:sub>9.3 (but not K<jats:sub>V<\/jats:sub>4.2) channel subunits in human isolated DSM cells. K<jats:sub>V<\/jats:sub>2.1 and K<jats:sub>V<\/jats:sub>2.2 protein expression was confirmed by Western blot analysis and immunocytochemistry. Perforated whole cell patch-clamp experiments revealed that ScTx1 (100 nM) inhibited the amplitude of the voltage step-induced K<jats:sub>V<\/jats:sub> current in freshly isolated human DSM cells. ScTx1 (100 nM) significantly increased the intracellular Ca<jats:sup>2+<\/jats:sup> level in DSM cells. In human DSM isolated strips, ScTx1 (100 nM) increased the spontaneous phasic contraction amplitude and muscle force, and enhanced the amplitude of the electrical field stimulation-induced contractions within the range of 3.5\u201330 Hz stimulation frequencies. These findings reveal that ScTx1-sensitive K<jats:sub>V<\/jats:sub>2-containing channels are key regulators of human DSM excitability and contractility and may represent new targets for pharmacological or genetic intervention for bladder dysfunction. <\/jats:p>","DOI":"10.1152\/ajpcell.00447.2011","type":"journal-article","created":{"date-parts":[[2012,3,15]],"date-time":"2012-03-15T07:34:11Z","timestamp":1331796851000},"page":"C1599-C1608","source":"Crossref","is-referenced-by-count":17,"title":["Expression and function of K<sub>V<\/sub>2-containing channels in human urinary bladder smooth muscle"],"prefix":"10.1152","volume":"302","author":[{"given":"Kiril L.","family":"Hristov","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, South Carolina; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, South Carolina; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serge A. 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