Voltage-gated ion channels and gating modifier toxins
Section snippets
The voltage-gated ion channels
Electrical signals control contraction of muscle, secretion of hormones, sensation of the environment, processing of information in the brain, and output from the brain to peripheral tissues. In excitable cells, electrical signals also have an important influence on intracellular metabolism and signal transduction, gene expression, protein synthesis and targeting, and protein degradation. In all of these contexts, electrical signals are conducted by members of the ion channel protein
Neurotoxins and sodium channels
Sodium channels are unique in that they are the molecular targets for several groups of neurotoxins, which strongly alter channel function by binding to several different receptor sites (Catterall, 1980; Cestèle and Catterall, 2000) Due to their high affinity and specificity, neurotoxins provide powerful tools to study the structure and the function of sodium channels, affecting both permeation and gating properties. Six different neurotoxin receptor sites have been identified on voltage-gated
The voltage-sensor trapping mechanism
Studies on sodium channels indicate that polypeptide neurotoxins from scorpions and sea anemones have evolved to use a novel voltage-sensor trapping mechanism to alter channel gating (Rogers et al., 1996; Cestèle et al., 1998, Cestèle et al., 2001). The voltage sensors responsible for sodium channel activation and its coupling to inactivation are transmembrane segments, inaccessible to binding of hydrophilic polypeptide toxins. To alter gating, these toxins have evolved to bind to the S3–S4
Conclusion
Voltage-gated Na+, Ca2+, and K+ channels are encoded by 60 genes in the human genome, and these channel proteins are the founding members of the larger superfamily of voltage-gated-like ion channels numbering 143 in total (Yu and Catterall, 2004). These channels have a common pore motif and a common mechanism for pore opening and voltage-dependent gating. Animals and plants from many phyla have targeted these channels with potent neurotoxins, which paralyze prey by altering electrical
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