Evidence 1
Activity
Activity
Neurotoxin
FUNCTION: Gating-modifier toxin that inhibits both sodium (Nav) and calcium (Cav3) channels by inducing hyperpolarizing shift in voltage-dependence of activation and steady state inactivation. Inhibits Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.6/SCN6A, Nav1.7/SCN9A and Cav3.1/CACNA1G sodium and calcium channels at nanomolar concentrations (IC(50)=81-301 nM). Surprisingly, selectively slows fast inactivation of Nav1.3/SCN3A. Also shows moderate inhibition of Cav3.2/CACNA1H calcium channels (IC(50)=1233 nM). Ex vivo, nearly ablates neuronal mechanosensitivity in afferent fibers innervating the colon and the bladder. In vivo, in a mouse model of irritable bowel syndrome, intracolonic administration of the toxin reverses colonic mechanical hypersensitivity. {ECO:0000269|PubMed:32826759}.
Target
voltage-gated sodium channel (Nav)
voltage-gated calcium channel (Cav)
Source & Reference
NA
UniProtKB/Swiss-Prot Tox-Prot
Other
Theraphosa apophysis (Goliath pinkfoot tarantula) (Pseudotheraphosa apophysis)
Neurotoxin
Calcium channel impairing toxin
Ion channel impairing toxin
Voltage-gated calcium channel impairing toxin
Voltage-gated sodium channel impairing toxin
Gating-modifier toxin that inhibits both sodium (Nav) and calcium (Cav3) channels by inducing hyperpolarizing shift in voltage-dependence of activation and steady state inactivation. Inhibits Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.6/SCN6A, Nav1.7/SCN9A and Cav3.1/CACNA1G sodium and calcium channels at nanomolar concentrations (IC(50)=81-301 nM).
Mu/omega-theraphotoxin-Tap1a (Mu/omega-TRTX-Tap1a)
spider
Neurotoxin 10 (Hwtx-1) family, 59 (Tltx) subfamily
Evidence at protein level
Calcium channel impairing toxin
Direct protein sequencing
Disulfide bond
Ion channel impairing toxin
Knottin
Neurotoxin
Pharmaceutical
Secreted
Toxin
Voltage-gated calcium channel impairing toxin
Voltage-gated sodium channel impairing toxin
TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|PubMed:32826759}.