English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
Add to Basket
 Local TagsRelease HistoryDetailsSummary
  A novel cross-species inhibitor to study the function of CatSper Ca2+ channels in sperm

Rennhack, A., Schiffer, C., Brenker, C., Fridman, D., Nitao, E. T., Cheng, Y.-M., et al. (2018). A novel cross-species inhibitor to study the function of CatSper Ca2+ channels in sperm. British Journal of Pharmacology, 175(15), 3144-3161. doi:10.1111/bph.14355.

Item is

 

show all hide all

Basic

show hide
Item Permalink: https://hdl.handle.net/21.11116/0000-0003-4B02-7 Version Permalink: https://hdl.handle.net/21.11116/0000-0008-807A-E
Genre: Journal Article

Files

show Files
hide Files
:
Rennhack_et_al-2018-British_Journal_of_Pharmacology.pdf (Any fulltext), 30MB
 
File Permalink:
-
Name:
Rennhack_et_al-2018-British_Journal_of_Pharmacology.pdf
Description:
-
OA-Status:
Visibility:
Private
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Locator:
https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.14355 (Abstract)
Description:
-
OA-Status:

Creators

show
hide
 Creators:
Rennhack, Andreas1, Author
Schiffer, Christian2, Author
Brenker, Christoph2, Author
Fridman, Dmitry1, Author
Nitao, Elis T.2, Author
Cheng, Yi-Min2, Author
Tamburrino, Lara2, Author
Balbach, Melanie1, Author
Stoelting, Gabriel2, Author
Berger, Thomas K.1, Author
Kierzek, Michelina2, Author
Alvarez, Luis1, Author
Wachten, Dagmar3, Author
Zeng, Xu-Hui2, Author
Baldi, Elisabetta2, Author
Publicover, Stephen J.2, Author
Kaupp, U. Benjamin1, Author
Struenker, Timo2, Author
Affiliations:
1Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society, Ludwig-Erhard-Allee 2, 53175 Bonn, DE, ou_2173679              
2External Organizations, ou_persistent22              
3Max Planck Research Group Molecular Physiology, Center of Advanced European Studies and Research (caesar), Max Planck Society, Ludwig-Erhard-Allee 2, 53175 Bonn, DE, ou_2173682              

Content

show
hide
Free keywords: -
 Abstract: BACKGROUND AND PURPOSE
Sperm 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 APPROACH
We 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 RESULTS
RU1968 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 IMPLICATIONS
We propose RU1968 as a novel tool to elucidate the function of CatSper channels in sperm across species.

Details

show
hide
Language(s): eng - English
 Dates: 2018
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000437671300007
DOI: 10.1111/bph.14355
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: British Journal of Pharmacology
  Abbreviation : Br J Pharmacol
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Houndmills, Basingstoke, Hampshire, etc. : Scientific & Medical Division, Macmillan Press, etc. ; Wiley
Pages: - Volume / Issue: 175 (15) Sequence Number: - Start / End Page: 3144 - 3161 Identifier: ISSN: 0007-1188
CoNE: https://pure.mpg.de/cone/journals/resource/110992357319090