Mutations, molecules, and myotonia

The linkages between a protein's primary sequence, three-dimensional structure, and the detailed manifestations of its function are well appreciated. Exploring and understanding these linkages have proven remarkably complex, however. While some functions may be localized exclusively to one protein region, others may be distributed or even diffusely coded in the structure. The kinetics of the tetrodotoxin-sensitive Na + channel and its voltage-gated siblings provide many examples of such complex and distributed coupling. The channel consists of four domains, each a repeat of the fundamental unit that is the primary motif of the voltage-dependent K + channel. In each domain, six membrane-spanning regions (S1-$6) give the channel its essential form, with charged groups embedded within these regions, presumably imparting the channel's