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Dendrotoxins: structure-activity relationships and effects on potassium ion channels

Harvey, A.L. and Robertson, Boyd (2004) Dendrotoxins: structure-activity relationships and effects on potassium ion channels. Current Medicinal Chemistry, 11 (23). pp. 3065-3072. ISSN 0929-8673

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Abstract

Dendrotoxins are small proteins isolated from mamba (Dendroaspis) snakes. The original dendrotoxin was found in venom of the Eastern green mamba, Dendroaspis angusticeps, and related proteins were subsequently found in other mamba venoms. The dendrotoxins contain 57-60 amino acid residues crosslinked by three disulphide bridges, and they are homologous to Kunitz-type serine protease inhibitors, such as aprotinin (BPTI). The dendrotoxins have little or no anti-protease activity, but they block particular subtypes of voltage-dependent potassium channels of the Kv1 subfamily in neurones. alpha-Dendrotoxin from green mamba Dendroaspis angusticeps and toxin I from the black mamba Dendroaspis polylepis block cloned Kv1.1, Kv1.2 and Kv1.6 channels in the low nanomolar range; toxin K, also from the black mamba Dendroaspis polylepis, preferentially blocks Kv1.1 channels and is active at picomolar concentrations. Structural modifications and mutations to dendrotoxins have helped to define the molecular recognition properties of different types of K+ channels, although more work is needed to characterise the chemical features of the toxins that underlie their selectivity and potency at particular subtypes of channels. Dendrotoxins have been useful markers of subtypes of K+ channels in vivo, and dendrotoxins have become widely used as probes for studying the function of K+ channels in physiology and pathophysiology. With some pathological conditions being associated with voltage-gated K+ channels, analogues of dendrotoxins might have therapeutic potential.

Item type: Article
ID code: 22256
Keywords: dendrotoxins, neurotoxins, potassium channels, transmitter release, synaptic transmission, snake venoms, episodic ataxia type-1, cerebellar purkinje-cells, root ganglion neurons, inhibitory postsynaptic currents, dendroaspis-polylepis-polylepis, site-directed mutagenesis, sensitive k+ channels, snake-venom toxins, green mamba venom, alpha-dendrotoxin, Zoology, Public aspects of medicine, Molecular Medicine, Pharmacology
Subjects: Science > Zoology
Medicine > Public aspects of medicine
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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Depositing user: Strathprints Administrator
Date Deposited: 09 Jul 2010 14:59
Last modified: 05 Sep 2014 04:43
URI: http://strathprints.strath.ac.uk/id/eprint/22256

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