000845551 001__ 845551
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000845551 0247_ $$2doi$$a10.1111/bph.14355
000845551 0247_ $$2ISSN$$a0007-1188
000845551 0247_ $$2ISSN$$a0366-0826
000845551 0247_ $$2ISSN$$a1476-5381
000845551 0247_ $$2pmid$$apmid:29723408
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000845551 1001_ $$0P:(DE-HGF)0$$aRennhack, Andreas$$b0
000845551 245__ $$aA novel cross-species inhibitor to study the function of CatSper Ca 2 + channels in sperm
000845551 260__ $$aMalden, MA$$bWiley$$c2018
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000845551 520__ $$aBackground 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.
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000845551 7001_ $$0P:(DE-Juel1)170068$$aSchiffer, Christian$$b1
000845551 7001_ $$0P:(DE-HGF)0$$aBrenker, Christoph$$b2
000845551 7001_ $$0P:(DE-Juel1)156436$$aFridman, Dmitry$$b3
000845551 7001_ $$0P:(DE-HGF)0$$aNitao, Elis T$$b4
000845551 7001_ $$0P:(DE-HGF)0$$aCheng, Yi-Min$$b5
000845551 7001_ $$0P:(DE-HGF)0$$aTamburrino, Lara$$b6
000845551 7001_ $$0P:(DE-Juel1)IHRS-BioSoft-140006$$aBalbach, Melanie$$b7
000845551 7001_ $$0P:(DE-Juel1)156347$$aStölting, Gabriel$$b8
000845551 7001_ $$0P:(DE-HGF)0$$aBerger, Thomas K$$b9
000845551 7001_ $$0P:(DE-HGF)0$$aKierzek, Michelina$$b10
000845551 7001_ $$0P:(DE-HGF)0$$aAlvarez, Luis$$b11
000845551 7001_ $$0P:(DE-HGF)0$$aWachten, Dagmar$$b12
000845551 7001_ $$0P:(DE-HGF)0$$aZeng, Xu-Hui$$b13
000845551 7001_ $$0P:(DE-HGF)0$$aBaldi, Elisabetta$$b14
000845551 7001_ $$0P:(DE-HGF)0$$aPublicover, Stephen$$b15
000845551 7001_ $$0P:(DE-Juel1)IHRS-BioSoft-20906$$aKaupp, Ulrich Benjamin$$b16
000845551 7001_ $$00000-0003-0812-1547$$aStrünker, Timo$$b17$$eCorresponding author
000845551 773__ $$0PERI:(DE-600)2029728-2$$a10.1111/bph.14355$$n15$$p3144-3161$$tBritish journal of pharmacology$$v175$$x0007-1188$$y2018
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