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@ARTICLE{Rennhack:845551,
      author       = {Rennhack, Andreas and Schiffer, Christian and Brenker,
                      Christoph and Fridman, Dmitry and Nitao, Elis T and Cheng,
                      Yi-Min and Tamburrino, Lara and Balbach, Melanie and
                      Stölting, Gabriel and Berger, Thomas K and Kierzek,
                      Michelina and Alvarez, Luis and Wachten, Dagmar and Zeng,
                      Xu-Hui and Baldi, Elisabetta and Publicover, Stephen and
                      Kaupp, Ulrich Benjamin and Strünker, Timo},
      title        = {{A} novel cross-species inhibitor to study the function of
                      {C}at{S}per {C}a 2 + channels in sperm},
      journal      = {British journal of pharmacology},
      volume       = {175},
      number       = {15},
      issn         = {0007-1188},
      address      = {Malden, MA},
      publisher    = {Wiley},
      reportid     = {FZJ-2018-02777},
      pages        = {3144-3161},
      year         = {2018},
      abstract     = {Background and PurposeSperm from many species share the
                      sperm‐specific Ca2+ channel CatSper that controls the
                      intracellular Ca2+ concentration and, thereby, the swimming
                      behaviour. A growing body of evidence suggests that the
                      mechanisms controlling the activity of CatSper and its role
                      during fertilization differ among species. A lack of
                      suitable pharmacological tools has hampered the elucidation
                      of the function of CatSper. Known inhibitors of CatSper
                      exhibit considerable side effects and also inhibit Slo3, the
                      principal K+ channel of mammalian sperm. The compound RU1968
                      was reported to suppress Ca2+ signaling in human sperm by an
                      unknown mechanism. Here, we examined the action of RU1968 on
                      CatSper in sperm from humans, mice, and sea
                      urchins.Experimental ApproachWe resynthesized RU1968 and
                      studied its action on sperm from humans, mice, and the sea
                      urchin Arbacia punctulata by Ca2+ fluorimetry, single‐cell
                      Ca2+ imaging, electrophysiology, opto‐chemistry, and
                      motility analysis.Key ResultsRU1968 inhibited CatSper in
                      sperm from invertebrates and mammals. The compound lacked
                      toxic side effects in human sperm, did not affect mouse
                      Slo3, and inhibited human Slo3 with about 15‐fold lower
                      potency than CatSper. Moreover, in human sperm, RU1968
                      mimicked CatSper dysfunction and suppressed motility
                      responses evoked by progesterone, an oviductal steroid known
                      to activate CatSper. Finally, RU1968 abolished
                      CatSper‐mediated chemotactic navigation in sea urchin
                      sperm.Conclusion and ImplicationsWe propose RU1968 as a
                      novel tool to elucidate the function of CatSper channels in
                      sperm across species.},
      cin          = {ICS-4},
      ddc          = {610},
      cid          = {I:(DE-Juel1)ICS-4-20110106},
      pnm          = {551 - Functional Macromolecules and Complexes (POF3-551) /
                      IHRS-BioSoft - International Helmholtz Research School of
                      Biophysics and Soft Matter (IHRS-BioSoft-20061101)},
      pid          = {G:(DE-HGF)POF3-551 / G:(DE-Juel1)IHRS-BioSoft-20061101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29723408},
      UT           = {WOS:000437671300007},
      doi          = {10.1111/bph.14355},
      url          = {https://juser.fz-juelich.de/record/845551},
}