MOLECULAR LOCALIZATION OF AN ION-BINDING SITE WITHIN THE PORE OF MAMMALIAN SODIUM-CHANNELS

被引:243
作者
BACKX, PH
YUE, DT
LAWRENCE, JH
MARBAN, E
TOMASELLI, GF
机构
[1] JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD 21205
[2] JOHNS HOPKINS UNIV,DEPT BIOMED ENGN,BALTIMORE,MD 21205
关键词
D O I
10.1126/science.1321496
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Sodium channels are the major proteins that underlie excitability in nerve, heart, and skeletal muscle. Chemical reaction rate theory was used to analyze the blockage of single wild-type and mutant sodium channels by cadmium ions. The affinity of cadmium for the native tetrodotoxin (TTX)-resistant cardiac channel was much higher than its affinity for the TTX-sensitive skeletal muscle isoform of the channel (mu-l). Mutation of Tyr401 to Cys, the corresponding residue in the cardiac sequence, rendered mu-l highly susceptible to cadmium blockage but resistant to TTX. The binding site was localized approximately 20% of the distance down the electrical field, thus defining the position of a critical residue within the sodium channel pore.
引用
收藏
页码:248 / 251
页数:4
相关论文
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