biostudies-literatureUnknown12Lorenz JTo locate and fertilize the egg, sperm probe the varying microenvironment prevailing at different stages during their journey across the female genital tract. To this end, they are equipped with a unique repertoire of mostly sperm-specific proteins. In particular, the flagellar Ca²⁺ channel CatSper has come into focus as a polymodal sensor used by human sperm to register ligands released into the female genital tract. Here, we provide the first comprehensive study on the pharmacology of the sperm-specific human Slo3 channel, shedding light on its modulation by reproductive fluids and their constituents. We show that seminal fluid and contained prostaglandins and Zn²⁺ do not affect the channel, whereas human Slo3 is inhibited in a non-genomic fashion by diverse steroidFrontiers in cell and developmental biology1275116https://www.ebi.ac.uk/biostudies/studies/S-EPMC11413451biostudies-literatureThe sperm-specific K⁺ channel Slo3 is inhibited by albumin and steroids contained in reproductive fluids.PMC11413451Mittermair TBehre HMLorenz JEisenhardt CKulle AENordhoff VBoenigk WFobker MBrenker CHolterhus PMStrunker TfalseThe sperm-specific K⁺ channel Slo3 is inhibited by albumin and steroids contained in reproductive fluids.To locate and fertilize the egg, sperm probe the varying microenvironment prevailing at different stages during their journey across the female genital tract. To this end, they are equipped with a unique repertoire of mostly sperm-specific proteins. In particular, the flagellar Ca²⁺ channel CatSper has come into focus as a polymodal sensor used by human sperm to register ligands released into the female genital tract. Here, we provide the first comprehensive study on the pharmacology of the sperm-specific human Slo3 channel, shedding light on its modulation by reproductive fluids and their constituents. We show that seminal fluid and contained prostaglandins and Zn²⁺ do not affect the channel, whereas human Slo3 is inhibited in a non-genomic fashion by diverse steroid2024-01-01T00:00:00Z20242026-04-30T00:05:09.305Z2025-04-06T13:21:44.708ZS-EPMC114134513931022710.3389/fcell.2024.1275116