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Sodium Channel Toxins - Receptor Targeting and Therapeutic Potential

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Sodium channels underlie propagated electrical signalling in most excitable cells, including neurons and the myocytes of skeletal muscle and heart. These proteins are targeted by a variety of current therapeutic drugs to combat such maladies as pain, myotonias, epilepsies and cardiac arrhythmias. Typically, these problems are associated with overactivity of sodium channels leading to hyperexcitability in the relevant tissue. More than ten distinct but closely related molecular isoforms of mammalian sodium channel are now known to be specifically expressed in different cell types and tissues. Therapeutic attenuation of sodium channel activity must be effected with great precision in both targeting and the degree of reduction in channel activity if a malfunction is to be corrected without introducing deleterious or even catastrophic side effects. Numerous natural toxins have evolved to target sodium channels, either by blocking current through the pore or by modifying channel gating. Among the well studied toxins, the peptide conotoxins from cone snail venoms show a remarkable ability to discriminate among closely related forms of sodium channel, as well as exhibiting a variety of modes of action. Here, we examine the molecular basis of action of different Na channel targeted conotoxins and explore their potential as models for the future design of more specifically targeted drugs.
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Keywords: cone snails; conopeptide; conotoxins; drug discovery; venoms; voltage-gated sodium channel

Document Type: Review Article

Affiliations: Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada T2N 4N1.

Publication date: 2004-12-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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