ウワバインを用いた薬理学的アプローチによる精子鞭毛運動の超活性化機序の解明

抄録

Mammalian sperm activate their motility upon ejaculation, but sperm motility needs further change to whiplash-like motility to penetrate and fertilize the egg. This specialized motility is called "hyperactivation". It was reported that extracellular Na⁺ is involved in regulation of hyperactivation. Na⁺/K⁺ ATPase (NKA) plays a major role in the regulation of cellular Na⁺ homeostasis. The catalytic subunit of NKA is an α subunit, and there are α1 and α4 subunits in sperm. The sensitivity of these two α subunits to ouabain, a specific NKA inhibitor, is quite different, that is, 10^-6 M ouabain inhibits NKA α4 while >10^-5 M ouabain inhibits both the α1 and α4. Therefore, this difference of sensitivity enables us to distinguish the physiological role of NKA α subunits on sperm function by pharmacological approach. In this symposium, I will introduce my latest study which showed, by utilizing this pharmacological property of ouabain, that the NKA α1 subunits is necessary for the maintenance of motility while the α4 subunit is necessary for the hyperactivation-associated change in flagellar movement. These results suggest that NKA α4 subunit is an attractive target for the male contraception.