The peptide toxin δ-hexatoxin-MrIX inhibits fast inactivation of NaVs in mouse cerebellar granule cells

This study has characterized a 44-amino acid peptide toxin, δ-hexatoxin-MrIX (δ-HXTX-MrIX), from the venom of the spider Macrothele raveni. δ-hexatoxin-MrIX potently inhibited the fast inactivation of NaVs in mouse cerebellar granule cells (CGCs) with an EC50 of 35.3 ± 5.9 nM. The toxin shifted both the steady-state activation and the steady-state inactivation curves of CGC NaVs to the hyperpolarized direction. δ-hexatoxin-MrIX also acted on NaV1.3 and NaV1.4 channels heterologously expressed in HEK293T cells, as well a s on NaVs in acutely isolated cockroach DUM neurons. However, the NaV1.5, NaV1.7 and NaV1.8 channels were resistant to δ-hexatoxin-MrIX. The toxin inhibited the fast inactivation of NaV1.3 and NaV1.4 with high affinity (EC50 values of 82.0 ± 3.0 nM and 24.0 ± 4.7 nM, respectively), but the saturating dose of toxin showed distinct efficacy on these two types of channels. δ-hexatoxin-MrIX is a peptide toxin acting on CGC NaVs and could be used as a pharmacological tool to explore the role of NaVs in granule cell maturation during cerebellum development.
Source: Peptides - Category: Biochemistry Source Type: research