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The essential calcium channel of sperm CatSper is temperature-gated

Author

Listed:
  • Dilip K. Swain

    (School of Medicine
    WashU Medicine)

  • Citlalli Vergara

    (School of Medicine
    WashU Medicine)

  • Júlia Castro-Arnau

    (School of Medicine
    WashU Medicine)

  • Polina V. Lishko

    (School of Medicine
    WashU Medicine
    WashU Medicine)

Abstract

The flagellar calcium channel CatSper is essential for male fertility, as it regulates calcium influx to trigger the hyperactive motility required for sperm to fertilize the egg. Precise activation of CatSper is critical, as premature activation can impair sperm function. While optimal temperature is known to influence fertilization, its effect on CatSper remains unknown. By directly recording from mouse spermatozoa, we reveal that CatSper functions as a temperature-gated ion channel, with a thermal threshold of 33.5 °C and a temperature coefficient Q10 of 5.1. Additionally, we show that physiological levels of spermine reversibly inhibit CatSper’s temperature gating, protecting against premature activation. Our findings highlight for the first time the presence of the temperature-gating modality of CatSper and reveal the protective role of spermine, a major component of seminal plasma. These results emphasize the need to maintain testes below 34 °C for optimal fertility and advance understanding of CatSper regulation in male fertility.

Suggested Citation

  • Dilip K. Swain & Citlalli Vergara & Júlia Castro-Arnau & Polina V. Lishko, 2025. "The essential calcium channel of sperm CatSper is temperature-gated," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58824-0
    DOI: 10.1038/s41467-025-58824-0
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    References listed on IDEAS

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    1. Yuriy Kirichok & Betsy Navarro & David E. Clapham, 2006. "Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel," Nature, Nature, vol. 439(7077), pages 737-740, February.
    2. Polina V. Lishko & Inna L. Botchkina & Yuriy Kirichok, 2011. "Progesterone activates the principal Ca2+ channel of human sperm," Nature, Nature, vol. 471(7338), pages 387-391, March.
    3. Dejian Ren & Betsy Navarro & Gloria Perez & Alexander C. Jackson & Shyuefang Hsu & Qing Shi & Jonathan L. Tilly & David E. Clapham, 2001. "A sperm ion channel required for sperm motility and male fertility," Nature, Nature, vol. 413(6856), pages 603-609, October.
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