Molecular hydrogen triggers TRPC4-TRPC4AP-dependent reversible calcium transients via extracellular influx - PubMed
3 days ago
- #TRPC4-TRPC4AP Axis
- #Molecular Hydrogen
- #Calcium Signaling
- Molecular hydrogen (H2) triggers reversible calcium transients via extracellular influx.
- H2 acts as a gaseous messenger, selectively opening plasma-membrane Ca2+ channels without causing cytotoxic overload.
- The study used real-time calcium imaging, CRISPR-Cas9 gene editing, and in vivo imaging in mice to monitor Ca2+ signals.
- H2-induced Ca2+ transients enhance cell motility, as confirmed by live-cell imaging and wound-healing assays.
- Protein-protein docking revealed a dual-arginine cluster in TRPC4's CIRB domain essential for H2-evoked Ca2+ influx.
- Mutating arginine residues in TRPC4 abolishes the H2-induced Ca2+ response.
- H2 triggers proton efflux and increases intracellular pH, modulating TRPC4-TRPC4AP binding forces.
- Transcriptomic analysis shows H2 activates calcium-related channels and promotes cytoskeletal remodeling and cell migration.
- The study identifies H2 as a novel gaseous signaling molecule regulating Ca2+ channels via the TRPC4-TRPC4AP axis.