Interaction between the sodium channel inactivation linker and domain III S4-S5

• Published in: Biophysical journal 1997-10, Vol.73 (4), p.1885-1895
• Main Authors: Smith, M.R., Goldin, A.L.
• Format: Article
• Language: English
• Subjects: Action Potentials; Amino Acid Sequence; Animals; Base Sequence; Binding Sites - genetics; Biophysical Phenomena; Biophysics; Brain - metabolism; DNA Primers - genetics; Female; In Vitro Techniques; Ion Channel Gating; Kinetics; Molecular Sequence Data; Mutagenesis, Site-Directed; Oocytes - metabolism; Rats; Sodium Channel Blockers; Sodium Channels - chemistry; Sodium Channels - genetics; Thermodynamics; Xenopus laevis
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(97)78219-5

The III-IV linker (L(III-IV)) of the rat brain sodium channel is critical for fast inactivation, possibly forming a fast inactivation particle. Inactivation can be disrupted by mutation of a conserved alanine at position 1329 in the S4-S5 loop of domain III. Combination of a charged mutation at 1329 with a compensatory (opposite) charge mutation at position 1489 in L(III-IV) partially restores inactivation of the channel. The compensatory charge mutant channel has a single-channel mean open time that is similar to that of the wild-type channel and is approximately 50 times shorter than that of the L(III-IV) mutant channel. The results of thermodynamic cycle analysis indicate that the mutations in domain III S4-S5 and L(III-IV) have a coupling energy of 2.8 kcal/mol, indicating that the two mutations act interdependently. These data suggest that L(III-IV) interacts directly with A1329, which may form part of the docking site if L(III-IV) is a fast inactivation particle.