• PMID: 29963982
• Gene Name: TRPV4
• Condition: Sperm hyperactivation
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Sperm hyperactivation

TRPV4 is the temperature-sensitive ion channel of human sperm

Mundt N, Spehr M, Lishko PV.

Ion channels control the ability of human sperm to fertilize the egg by triggering hyperactivated motility, which is regulated by membrane potential, intracellular pH, and cytosolic calcium. Previous studies unraveled three essential ion channels that regulate these parameters: (1) the Ca(2+) channel CatSper, (2) the K(+) channel KSper, and (3) the H(+) channel Hv1. However, the molecular identity of the sperm Na(+) conductance that mediates initial membrane depolarization and, thus, triggers downstream signaling events is yet to be defined. Here, we functionally characterize DSper, the Depolarizing Channel of Sperm, as the temperature-activated channel TRPV4. It is functionally expressed at both mRNA and protein levels, while other temperature-sensitive TRPV channels are not functional in human sperm. DSper currents are activated by warm temperatures and mediate cation conductance, that shares a pharmacological profile reminiscent of TRPV4. Together, these results suggest that TRPV4 activation triggers initial membrane depolarization, facilitating both CatSper and Hv1 gating and, consequently, sperm hyperactivation. CI - © 2018, Mundt et al. FAU - Mundt, Nadine AU - Mundt N AUID- ORCID: 0000-0003-3370-2933 AD - Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States. AD - Department of Chemosensation, Institute for Biology II, RWTH Aachen University, Aachen, Germany. FAU - Spehr, Marc AU - Spehr M AUID- ORCID: 0000-0001-6616-4196 AD - Department of Chemosensation, Institute for Biology II, RWTH Aachen University, Aachen, Germany.