Interaction between the sodium channel inactivation linker and domain III S4-S5.
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.
Smith
M R
MR
Department of Microbiology and Molecular Genetics, University of California, Irvine 92697-4025, USA.
Goldin
A L
AL
D000200:Action Potentials; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D055592:Biophysical Phenomena; D001703:Biophysics; D001921:Brain / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics; D014982:Xenopus laevis
D017931:DNA Primers; D026941:Sodium Channel Blockers; D015222:Sodium Channels