MECHANISM OF HUMAN SPERM ACTIVATION BY EXTRACELLULAR ATP

We have identified the mechanism whereby extracellular ATP (ATP(e)) tr iggers the acrosome reaction in human spermatozoa. This nucleotide ope ns a ligand-gated ion channel expressed on the sperm plasma membrane. ATP(e) threshold and 50% effective concentration calculated on the tot al added ATP(e) are 0.1 and 2 mM, respectively, corresponding to a fre e ATP concentration (ATP(4-)) of 3 and 200 mu M, respectively. The ATP (e)-gated channel is selective for monovalent cations (Na+, choline, a nd methylglucamine), whereas on the contrary, permeability to Ca2+ is negligible. Isosmolar replacement of extracellular Na+ with sucrose fu lly blocked ATP(e)-dependent sperm activation, thus suggesting a manda tory role for Na+ influx. These results show that human sperm express an ATP(e)-gated Na+ channel that might have an important role in sperm activation before egg fertilization.