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Science 10 July 1992:
Vol. 257. no. 5067, pp. 248 - 251
DOI: 10.1126/science.1321496
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Articles

Science, Vol 257, Issue 5067, 248-251
Copyright © 1992 by American Association for the Advancement of Science

articles

Molecular localization of an ion-binding site within the pore of mammalian sodium channels

PH Backx, DT Yue, JH Lawrence, E Marban, and GF Tomaselli

Department of Medicine, Johns Hopkins University, Baltimore, MD 21205.

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 (microliters). Mutation of Tyr401 to Cys, the corresponding residue in the cardiac sequence, rendered microliters 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.


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