In human spermatozoa, progesterone (P-4) induces a depolarization of the pl
asma membrane, a rapid calcium (Ca2+) influx, and a chloride efflux, The so
dium ion (Na+) was partly responsible for the P-4-induced depolarizing effe
ct but was not required for calcium influx, We used fluorescent probes for
spectrofluorometry to investigate whether P-4 induced a Na+ influx and whet
her voltage-operated channels were involved in Na+ and/ or Ca2+ entries, We
found that 10 mu M P, significantly increased intracellular Na+ concentrat
ion from 17,8 +/- 2.0 mM to 27.2 +/- 1.6 mM (P < 0,001), Prior incubation o
f spermatozoa with 10 mu M flunarizine, a Na+ and Ca2+ voltage-dependent ch
annel blocker, inhibited the sodium influx induced by 10 mu M P-4 by 84.6 /- 15.4%. The Ca2+ influx induced by 10 mu M P-4 was also significantly inh
ibited in a Na+-containing medium by 10 mu M flunarizine or 10 mu M pimozid
e (P < 0.01). In contrast, flunarizine had no inhibitory effect on the Ca2 influx induced by 10 mu M P-4 in spermatozoa incubated in Na+-depleted med
ium. The P-4-promoted acrosome reaction (AR) was significantly higher when
spermatozoa were incubated in Na+-containing medium as compared to Na+-depl
eted medium, These data demonstrate that P-4 stimulates a Na+ influx that c
ould be involved in the AR completion, They also suggest that voltage-depen
dent Na+ and Ca2+ channels are implicated in P-4-mediated signaling pathway
in human spermatozoa.