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The μO‐conotoxin MrVIA inhibits voltage‐gated sodium channels by associating with domain‐3
Author(s) -
Zorn Stefan,
Leipold Enrico,
Hansel Alfred,
Bulaj Grzegorz,
Olivera Baldomero M.,
Terlau Heinrich,
Heinemann Stefan H.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.01.057
Subject(s) - conotoxin , sodium channel , chemistry , sodium , biophysics , biology , biochemistry , venom , organic chemistry
Several families of peptide toxins from cone snails affect voltage‐gated sodium (Na V ) channels: μ‐conotoxins block the pore, δ‐conotoxins inhibit channel inactivation, and μO‐conotoxins inhibit Na V channels by an unknown mechanism. The only currently known μO‐conotoxins MrVIA and MrVIB from Conus marmoreus were applied to cloned rat skeletal muscle (Na V 1.4) and brain (Na V 1.2) sodium channels in mammalian cells. A systematic domain‐swapping strategy identified the C‐terminal pore loop of domain‐3 as the major determinant for Na V 1.4 being more potently blocked than Na V 1.2 channels. μO‐conotoxins therefore show an interaction pattern with Na V channels that is clearly different from the related μ‐ and δ‐conotoxins, indicative of a distinct molecular mechanism of channel inhibition.