Fig. 1.

A, transmembrane topology of the Na⁺ channel. Arrows indicated the P segments, the regions between the fifth and sixth membrane spanning repeats. The residues that were mutated are proximal to the selectivity filter and are shown below the topology cartoon. The putative selectivity residues Asp400, Glu755, Lys1237, and A1529 are enclosed in the box. Cysteine mutants at all positions except Asp400 and Lys1237 (both in italic) were examined. Gly754 and Leu752 are labeled with a strikethrough due to nonexpression of cysteine mutants. B and C, normalized activation curves (B) and steady-state inactivation curves (C) for the wild-type and domain I-IV mutants. The solid curves are fits to a Boltzmann function as described under Materials and Methods. The parameters of the fits are summarized in Table 1.