Evidence 1
Activity
Activity
Neurotoxin
FUNCTION: Gating-modifier toxin that potently inhibits inactivation of the mammalian Nav1.1/SCN1A sodium channel (EC(50)=38 nM) (PubMed:27281198, PubMed:30076230). Also moderately inhibits inactivation of Nav1.2/SCN2A (EC(50)=236 nM) and Nav1.3/SCN3A (EC(50)=220 nM) when the channels are expressed in oocytes without the beta-1 auxiliary subunit (PubMed:27281198). Does not inhibit inactivation of Nav1.2/SCN2A when the channel is coexpressed with the beta-1 auxiliary subunit (PubMed:30076230). When tested on Nav1.1/SCN1A channel, it enhances peak current amplitude and potently delays channel inactivation in a dose-dependent manner, leading to a large sustained current (PubMed:30076230). It has no effect on the voltage-dependence of steady-state activation, and induces a depolarizing shift in the voltage dependence of inactivation (PubMed:30076230). In addition, it does not modify the recovery from fast inactivation in Nav1.1/SCN1A (PubMed:30076230). The binding affinity and subtype selectivity of the toxin towards Nav1.1/SCN1A channel is determined by residues within both the S1-S2 and S3-S4 loops of the domain IV voltage sensor of the channel (PubMed:27281198). This toxin also weakly inhibits several subtypes of voltage-gated potassium channels (PubMed:27281198). It moderately blocks Kv2.1/KCNB1 (23% inhibition at 100 nM), Kv2.2/KCNB2 (19.7% at 100 nM and 51% at 300 nM), Kv4.1/KCND1 (IC(50)=280 nM), Kv4.2/KCND2 (39% at 300 nM) and Kv4.3/KCND3 (43% at 300 nM) (PubMed:12065754). In vivo, intracerebroventricular injection into mice elicits convulsions, spasms, tremors and rapid death (PubMed:12065754). When injected into mouse hindpaw, the toxin elicits an immediate and robust response to pain (PubMed:27281198). However, intraplantar injection of toxin does not cause neurogenic inflammation or alter sensitivity to heat, indicative of a modality-specific effect on mechanosensitive neurons (PubMed:27281198). In Dravet syndrome mice model, intracerebroventricular infusion of this peptide rescues mice from seizures and premature death (PubMed:30076230). {ECO:0000269|PubMed:12065754, ECO:0000269|PubMed:27281198, ECO:0000269|PubMed:30076230}.
Target
voltage-gated sodium channel (Nav)
voltage-gated potassium channel (Kv)
Source & Reference
NA
UniProtKB/Swiss-Prot Tox-Prot
Other
Heteroscodra maculata (Togo starburst tarantula) (Togo starburst baboon spider)
Neurotoxin
Ion channel impairing toxin
Potassium channel impairing toxin
Voltage-gated potassium channel impairing toxin
Voltage-gated sodium channel impairing toxin
Gating-modifier toxin that potently inhibits inactivation of the mammalian Nav1.1/SCN1A sodium channel (EC(50)=38 nM) (PubMed:27281198, PubMed:30076230). Also moderately inhibits inactivation of Nav1.2/SCN2A (EC(50)=236 nM) and Nav1.3/SCN3A (EC(50)=220 nM) when the channels are expressed in oocytes without the beta-1 auxiliary subunit (PubMed:27281198).
Delta-theraphotoxin-Hm1a (Delta-TRTX-Hm1a) (Heteroscodratoxin-1) (HmTx1) (Kappa-theraphotoxin-Hm1a) (Kappa-TRTX-Hm1a)
spider
Neurotoxin 10 (Hwtx-1) family, 09 (HaTx) subfamily
Evidence at protein level
3D-structure
Direct protein sequencing
Disulfide bond
Ion channel impairing toxin
Knottin
Neurotoxin
Pharmaceutical
Potassium channel impairing toxin
Secreted
Toxin
Voltage-gated potassium channel impairing toxin
Voltage-gated sodium channel impairing toxin
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:12065754, ECO:0000305|PubMed:27281198}.