{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:08:04Z","timestamp":1790150884731,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,2,24]],"date-time":"2012-02-24T00:00:00Z","timestamp":1330041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Voltage\u2010dependent calcium channels are widely distributed in animal cells, including spermatozoa. Calcium is fundamental in many sperm functions such as: motility, capacitation, and the acrosome reaction (AR), all essential for fertilization. Pharmacological evidence has suggested T\u2010type calcium channels participate in the AR. Niflumic acid (NA), a non\u2010steroidal anti\u2010inflammatory drug commonly used as chloride channel blocker, blocks T\u2010currents in mouse spermatogenic cells and Cl<jats:sup>\u2212<\/jats:sup>channels in testicular sperm. Here we examine the mechanism of NA blockade and explore if it can be used to separate the contribution of different Ca<jats:sub>V<\/jats:sub>3 members previously detected in these cells. Electrophysiological patch\u2010clamp recordings were performed in isolated mouse spermatogenic cells and in HEK cells heterologously expressing Ca<jats:sub>V<\/jats:sub>3 channels. NA blocks mouse spermatogenic cell T\u2010type currents with an IC<jats:sub>50<\/jats:sub>of 73.5\u2009\u00b5M, without major voltage\u2010dependent effects. The NA blockade is more potent in the open and in the inactivated state than in the closed state of the T\u2010type channels. Interestingly, we found that heterologously expressed Ca<jats:sub>V<\/jats:sub>3.1 and Ca<jats:sub>V<\/jats:sub>3.3 channels were more sensitive to NA than Ca<jats:sub>V<\/jats:sub>3.2 channels, and this drug substantially slowed the recovery from inactivation of the three isoforms. Molecular docking modeling of drug\u2010channel binding predicts that NA binds preferentially to the extracellular face of Ca<jats:sub>V<\/jats:sub>3.1 channels. The biophysical characteristics of mouse spermatogenic cell T\u2010type currents more closely resemble those from heterologously expressed Ca<jats:sub>V<\/jats:sub>3.1 channels, including their sensitivity to NA. As Ca<jats:sub>V<\/jats:sub>3.1 null mice maintain their spermatogenic cell T\u2010currents, it is likely that a novel Ca<jats:sub>V<\/jats:sub>3.2 isoform is responsible for them. J. Cell. Physiol. 227: 2542\u20132555, 2012. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22992","type":"journal-article","created":{"date-parts":[[2011,8,31]],"date-time":"2011-08-31T23:49:59Z","timestamp":1314834599000},"page":"2542-2555","source":"Crossref","is-referenced-by-count":35,"title":["Niflumic acid blocks native and recombinant T\u2010type channels"],"prefix":"10.1002","volume":"227","author":[{"given":"Enrique","family":"Balderas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogelio","family":"Ateaga\u2010Tlecuitl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Rivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan 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