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Updated: Aug 24, 2026

Recording Electrical Currents across the Plasma Membrane of Mammalian Sperm Cells
Published on: February 14, 2021
Plasma membrane Ca2+ ATPase 4 is required for sperm motility and male fertility
Kai Schuh1, Elizabeth J Cartwright, Eriks Jankevics
1Institute for Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Josef-Schneider-Strasse 2, D-97080 Wuerzburg, Germany. schuh_k@klinik.uni-wuerzburg.de
Abstract:
Calcium and Ca(2+)-dependent signals play a crucial role in sperm motility and mammalian fertilization, but the molecules and mechanisms underlying these Ca(2+)-dependent pathways are incompletely understood. Here we show that homozygous male mice with a targeted gene deletion of isoform 4 of the plasma membrane calcium/calmodulin-dependent calcium ATPase (PMCA), which is highly enriched in the sperm tail, are infertile due to severely impaired sperm motility. Furthermore, the PMCA inhibitor 5-(and-6)-carboxyeosin diacetate succinimidyl ester reduced sperm motility in wild-type animals, thus mimicking the effects of PMCA4 deficiency on sperm motility and supporting the hypothesis of a pivotal role of the PMCA4 on the regulation of sperm function and intracellular Ca(2+) levels.
Insights
Plasma membrane calcium ATPase 4 (PMCA4) is essential for sperm motility and male fertility. PMCA4 deficiency in mice causes infertility and impaired sperm function, highlighting its critical role in regulating intracellular calcium levels.
Area of Science:
- Reproductive biology
- Cellular physiology
- Biochemistry
Background:
- Calcium ions (Ca2+) and Ca2+-dependent signals are vital for sperm motility and fertilization.
- The specific molecular mechanisms governing these Ca2+ pathways in sperm remain incompletely understood.
Purpose of the Study:
- To investigate the role of plasma membrane calcium/calmodulin-dependent calcium ATPase (PMCA) isoform 4 in sperm function and male fertility.
- To elucidate the contribution of PMCA4 to the regulation of intracellular Ca2+ levels in sperm.
Main Methods:
- Generation and analysis of homozygous male mice with a targeted gene deletion of the PMCA4 gene.
- Assessment of sperm motility in wild-type and PMCA4-deficient mice.
- Pharmacological inhibition of PMCA activity in wild-type sperm using 5-(and-6)-carboxyeosin diacetate succinimidyl ester.
Main Results:
- Homozygous male mice lacking PMCA4 were infertile, exhibiting severely impaired sperm motility.
- PMCA4 is highly enriched in the sperm tail.
- Inhibition of PMCA activity in wild-type sperm recapitulated the motility defects observed in PMCA4-deficient mice.
Conclusions:
- PMCA4 plays a pivotal role in regulating sperm function, particularly motility.
- PMCA4 is critical for maintaining appropriate intracellular Ca2+ levels necessary for mammalian fertilization.
- Targeting PMCA4 represents a potential strategy for understanding and addressing male infertility.
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05:44Medium-throughput Screening Assays for Assessment of Effects on Ca2+-Signaling and Acrosome Reaction in Human Sperm
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