dGNaC1, a gonad-specific amiloride-sensitive Na+ channel

被引:39
作者
Darboux, I [1 ]
Lingueglia, E [1 ]
Champigny, G [1 ]
Coscoy, S [1 ]
Barbry, P [1 ]
Lazdunski, M [1 ]
机构
[1] CNRS, Inst Pharmacol Mol & Cellulaire, UPR 411, F-06560 Valbonne, France
关键词
D O I
10.1074/jbc.273.16.9424
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu M), benzamil (IC50 = 2 mu M), and ethylisopropyl amiloride (IC50 = 49 mu M). These properties are clearly different from those obtained after expression of the previously cloned members of this family, including ENaC and the human alpha ENaC-like subunit, delta NaC. 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.
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收藏
页码:9424 / 9429
页数:6
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