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

A.L. Harvey, Boyd Robertson

Research output: Contribution to journalArticlepeer-review

114 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)3065-3072
Number of pages7
JournalCurrent Medicinal Chemistry
Issue number23
Publication statusPublished - Dec 2004


  • 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


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