Darboux I, Lingueglia E, Champigny G, Coscoy S, Barbry P, Lazdunski M
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
J Biol Chem. 1998 Apr 17;273(16):9424-9. doi: 10.1074/jbc.273.16.9424.
Amiloride-sensitive sodium channels have been implicated in reproductive and early developmental processes of several species. These include the fast block of polyspermy in Xenopus oocytes that follows the sperm binding to the egg or blastocoel expansion in mammalian embryo. We have now identified a gene called dGNaC1 that is specifically expressed in the gonads and early embryo in Drosophila melanogaster. The corresponding protein belongs to the superfamily of cationic channels blocked by amiloride that includes Caenorhabditis elegans degenerins, the Helix aspersa FMRF-amide ionotropic receptor (FaNaC), the mammalian epithelial Na+ channel (ENaC), and acid-sensing ionic channels (ASIC, DRASIC, and MDEG). Expression of dGNaC1 in Xenopus oocytes generates a constitutive current that does not discriminate between Na+ and Li+, but is selective for Na+ over K+. This current is blocked by amiloride (IC50 = 24 microM), benzamil (IC50 = 2 microM), and ethylisopropyl amiloride (IC50 = 49 microM). These properties are clearly different from those obtained after expression of the previously cloned members of this family, including ENaC and the human alphaENaC-like subunit, deltaNaC. Interestingly, the pharmacology of dGNaC1 is not very different from that found for the Na+ channel characterized in rabbit preimplantation embryos. We postulate that this channel may participate in gametogenesis and early embryonic development in Drosophila.
氨氯地平敏感的钠通道与几种物种的生殖和早期发育过程有关。这些过程包括非洲爪蟾卵母细胞中精子与卵子结合后对多精入卵的快速阻断，以及哺乳动物胚胎中的囊胚腔扩张。我们现已鉴定出一个名为dGNaC1的基因，它在黑腹果蝇的性腺和早期胚胎中特异性表达。相应的蛋白质属于被氨氯地平阻断的阳离子通道超家族，该家族包括秀丽隐杆线虫的退化蛋白、光滑双脐螺FMRF酰胺离子型受体（FaNaC）、哺乳动物上皮钠通道（ENaC）以及酸敏感离子通道（ASIC、DRASIC和MDEG）。dGNaC1在非洲爪蟾卵母细胞中的表达产生一种组成性电流，该电流对Na⁺和Li⁺没有区分，但对Na⁺的选择性高于K⁺。这种电流被氨氯地平（IC50 = 24 microM）、苄甲氯铵（IC50 = 2 microM）和乙基异丙基氨氯地平（IC50 = 49 microM）阻断。这些特性明显不同于该家族先前克隆成员（包括ENaC和人类αENaC样亚基deltaNaC）表达后所获得的特性。有趣的是，dGNaC1的药理学特性与在兔植入前胚胎中所表征的钠通道的药理学特性并没有太大差异。我们推测该通道可能参与果蝇的配子发生和早期胚胎发育。
