RT Journal Article
SR Electronic
T1 TRPV4 is the temperature-sensitive ion channel of human sperm
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 268409
DO 10.1101/268409
A1 Nadine Mundt
A1 Marc Spehr
A1 Polina V. Lishko
YR 2018
UL http://biorxiv.org/content/early/2018/02/20/268409.abstract
AB Ion channels control sperm fertilizing ability 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 Ca2+ channel CatSper, 2) the K+ channel KSper, and 3) the H+ channel Hv1. However, the molecular identity of an additional 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.