ARC Future Fellow
The University of Queensland
(61) 7 334-62021
Rethinking Voltage-Gated Sodium Channel Inhibition
Voltage-gated sodium channels, NaV, are integral in almost all aspects of human physiology, including cardiac and muscle function and pain perception, and sodium channel subtype NaV1.7 have been genetically validated to be involved in nociception. Peptide toxins isolated from venomous creatures are potent inhibitors of human voltage-gated sodium channels and venom peptides selective against NaV1.7 are showing great potential as therapeutic pain leads, inhibiting NaV activity by blocking the pore domain, pore blockers, or by binding to the membrane-embedded voltage sensor domain of the sodium channel, gating-modifier toxins.
However, despite intensive research efforts into NaV1.7 inhibitors there has been little in the way of translation probably due to our lack of understanding how to achieve subtype selectivity and complete block of the NaV1.7 subtype and how to move from effective in vitro to in vivo inhibitors.
We are delineating the mechanism of action behind venom peptide inhibition of voltage-gated sodium channel on a molecular and global level in order to engineer peptides achieving subtype specific and complete inhibition of this therapeutically relevant sodium channel subtype to ultimately unlock the potential of these potent venom peptides as therapeutic leads for the treatment of pain.
AuthorsChristina I. Schroeder
AffiliationsInstitute for Molecular Bioscience, The University of Queensland, Brisbane, 4072, Qld, Australia