Heteropodatoxin
Encyclopedia
Heteropodatoxins are peptide
toxins from the venom of the giant crab spider Heteropoda venatoria, which block Kv4.2 voltage-gated potassium channel
s.
These three toxins are structurally similar peptides of 29-32 amino acids . They show sequence similarity to Hanatoxins, which can be isolated from the venom of the Chilean rose tarantula
Grammostola rosea .
s. All three toxins have been shown to block the potassium channel Kv4.2 . Recombinant heteropodatoxin-2 blocks the potassium channels Kv4.1, Kv4.2 and Kv4.3, but not Kv1.4, Kv2.1, or Kv3.4 .
modifier of the Kv4.2 channels . It shifts the voltage dependence of the activation
and the inactivation of the Kv4.3 potassium channel
to more positive values. As a result, in the presence of the toxin this channel has a higher probability of being inactivated and a larger depolarization is needed to open the channel. However, heterpodatoxin-2 did not affect the voltage dependence of the Kv4.1 channel, suggesting that the precise mechanism of block remains to be elucidated and a role as a pore blocker cannot be excluded . The voltage dependence of Kv4.2 block varies among the three different heteropodatoxins. It is less voltage dependent for HpTx1 than for HpTx2 or HpTx3 .
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
toxins from the venom of the giant crab spider Heteropoda venatoria, which block Kv4.2 voltage-gated potassium channel
Voltage-gated potassium channel
Voltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state....
s.
Source
Heteropodatoxins are purified from the venom of the giant crab spider, Heteropoda venatoria .Chemistry
Heteropodatoxins contain an Inhibitory Cystin Knot (ICK) motif, which consist of a compact disulfide-bonded core, from which four loops emerge . There are three different heteropodatoxins :- heteropodatoxin-1, also known as Toxin AU3/KJ5 or HpTx1
- heteropodatoxin-2, also known as Toxin KJ6 or HpTx2
- heteropodatoxin-3, also known as Toxin AU5C/KJ7 or HpTx3
These three toxins are structurally similar peptides of 29-32 amino acids . They show sequence similarity to Hanatoxins, which can be isolated from the venom of the Chilean rose tarantula
Chilean rose tarantula
The Chilean rose tarantula , also known as the Chilean flame tarantula, Chilean fire tarantula or the Chilean red-haired tarantula or the Chilean rose hair tarantula , is probably the most common species of tarantula available in pet stores today, due to the large number of wild-caught specimens...
Grammostola rosea .
Target
Heteropodatoxins block A-type, transient voltage-gated potassium channelVoltage-gated potassium channel
Voltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state....
s. All three toxins have been shown to block the potassium channel Kv4.2 . Recombinant heteropodatoxin-2 blocks the potassium channels Kv4.1, Kv4.2 and Kv4.3, but not Kv1.4, Kv2.1, or Kv3.4 .
Mode of action
Heterpodatoxin-2 most likely acts as a gatingGating
-Neurobiology:*Gating , the opening or closing of ion channels*Sensory gating, an automatic process by which the brain adjusts to stimuli*Synaptic gating, neural circuits suppressing inputs through synapses...
modifier of the Kv4.2 channels . It shifts the voltage dependence of the activation
Activation
Activation in chemical sciences generally refers to the process whereby something is prepared or excited for a subsequent reaction.- Chemistry :...
and the inactivation of the Kv4.3 potassium channel
Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...
to more positive values. As a result, in the presence of the toxin this channel has a higher probability of being inactivated and a larger depolarization is needed to open the channel. However, heterpodatoxin-2 did not affect the voltage dependence of the Kv4.1 channel, suggesting that the precise mechanism of block remains to be elucidated and a role as a pore blocker cannot be excluded . The voltage dependence of Kv4.2 block varies among the three different heteropodatoxins. It is less voltage dependent for HpTx1 than for HpTx2 or HpTx3 .