Three peptide modulators of the human voltage-gated sodium channel 1.7, an important analgesic target, from venom of an Australian tarantula

Chow, Chun Yuen, Cristofori-Armstrong, Ben, Undheim, Eivind A. B., King, Glenn F. and Rash, Lachlan D. (2015) Three peptide modulators of the human voltage-gated sodium channel 1.7, an important analgesic target, from venom of an Australian tarantula. Toxins, 7 7: 2494-2513. doi:10.3390/toxins7072494

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Author Chow, Chun Yuen
Cristofori-Armstrong, Ben
Undheim, Eivind A. B.
King, Glenn F.
Rash, Lachlan D.
Title Three peptide modulators of the human voltage-gated sodium channel 1.7, an important analgesic target, from venom of an Australian tarantula
Journal name Toxins   Check publisher's open access policy
ISSN 2072-6651
Publication date 2015-06-30
Year available 2015
Sub-type Article (original research)
DOI 10.3390/toxins7072494
Open Access Status DOI
Volume 7
Issue 7
Start page 2494
End page 2513
Total pages 20
Place of publication Basel, Switzerland
Publisher MDPI
Collection year 2016
Language eng
Formatted abstract
Voltage-gated sodium (NaV) channels are responsible for propagating action potentials in excitable cells. NaV1.7 plays a crucial role in the human pain signalling pathway and it is an important therapeutic target for treatment of chronic pain. Numerous spider venom peptides have been shown to modulate the activity of NaV channels and these peptides represent a rich source of research tools and therapeutic lead molecules. The aim of this study was to determine the diversity of NaV1.7-active peptides in the venom of an Australian Phlogius sp. tarantula and to characterise their potency and subtype selectivity. We isolated three novel peptides, μ-TRTX-Phlo1a, -Phlo1b and -Phlo2a, that inhibit human NaV1.7 (hNaV1.7). Phlo1a and Phlo1b are 35-residue peptides that differ by one amino acid and belong in NaSpTx family 2. The partial sequence of Phlo2a revealed extensive similarity with ProTx-II from NaSpTx family 3. Phlo1a and Phlo1b inhibit hNaV1.7 with IC50 values of 459 and 360 nM, respectively, with only minor inhibitory activity on rat NaV1.2 and hNaV1.5. Although similarly potent at hNaV1.7 (IC50 333 nM), Phlo2a was less selective, as it also potently inhibited rNaV1.2 and hNaV1.5. All three peptides cause a depolarising shift in the voltage-dependence of hNaV1.7 activation.
Keyword Phlogius sp
Spider venom
Venom peptide
Voltage gated sodium channel
Ion channel
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 09 Jul 2015, 10:57:14 EST by Susan Allen on behalf of Institute for Molecular Bioscience