Max Planck Institute for Dynamics and Self-Organization -- Department for Nonlinear Dynamics and Network Dynamics Group
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BCCN AG-Seminar

Tuesday, 20.12.2005 16 c.t.

Modulation of Sodium Channel Function by Voltage-Sensor Toxins

by Prof. Dr. Stefan H. Heinemann
from Molekulare und zelluläre Biophysik, Klinikum der Friedrich-Schiller-Universität Jena

Contact person: Fred Wolf


Seminarraum Haus 2, 4. Stock (Bunsenstr.)


Voltage-gated sodium channels (NaV channels) are large transmembrane proteins mainly composed of a four-domain -subunit forming the channel complex. These channels initiate action potentials by a complex depolarization-triggered activation (opening) and subsequent inactivation (closing) of the channel pore. The major molecular elements involved in these processes are the voltage sensors, i.e. the positively charged S4 segments in all four domains. NaV channels are targets of various neurotoxins. According to their binding to the channel protein and the quality of their effects such toxins are classified with respect to so-called receptor sites (1-10). Mammals express nine different NaV channel genes, some of them showing almost indistinguishable functional properties. We have studied in detail the effects of peptide toxins from venoms of scorpions (-toxins acting on site-3 and -toxins acting on site-4) and cone snails (-conotoxins acting on site-6 and µ-O-conotoxins acting on an yet unknown site). The experimental approach was to assay the effects of such biotoxins on various NaV channel isoforms upon functional expression in mammalian cells to unravel a subtype specificity of these toxins. By formation of channel chimeras and by introduction of single-residue changes the interaction sites with NaV channels were mapped to voltage-sensor elements. Quantitative analysis of single-cell data provides insight into the molecular mechanism of how the toxins interact with the voltage sensors of NaV channels. As a result it can be shown that toxins with very different structures exerting quite diverse functional effects on NaV channels work according to a common molecular mechanism.

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