ω-Agatoxin IVA TFA

ω-Agatoxin IVA TFA is the trifluoroacetate salt form of ω-Agatoxin IVA (CAS No. 145017-83-0). As a peptide toxin derived from the venom of funnel-web spiders, its core biological function is the specific blocking of P/Q-type voltage-gated calcium channels (Cav2.1), with a weak blocking effect on N-type calcium channels (partial inhibition at 1 μM) and no influence on L-type or T-type calcium channels. It can inhibit the release of neurotransmitters (glutamate, GABA), exert anticonvulsant and neuroprotective effects, and mediate the nicotinic activation regulation of cardiac vagal neurons. The IC50 value is subtype/splice variant-specific: 1-2 nM for P-type Cav2.1 (without the NP motif) and increased to 270.5±1.1 nM for Q-type Cav2.1 (with the NP motif), with an overall IC50 range of 2-1000 nM. Common application concentrations: 100 nM-1 μM in in vitro cell experiments (e.g., neuronal calcium current recording, synaptic transmission research); 0.01-1 nM via intracerebroventricular injection (acute epilepsy model) and 0.1-0.5 nM via intraperitoneal injection (epilepsy kindling model) in animal experiments; 0.5 nM for EEG monitoring of epileptiform discharges. Effective therapeutic concentrations correspond to animal models: 0.5 nM intracerebroventricular injection can significantly prolong the latency of epileptic seizures, and 0.1-0.5 nM intraperitoneal injection can inhibit epilepsy progression, reduce intracerebral apoptosis (decrease cleaved caspase-3 expression) and increase BDNF expression without affecting motor coordination.

References:

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[4] Wang J, Irnaten M, Mendelowitz D. Agatoxin-IVA-sensitive calcium channels mediate the presynaptic and postsynaptic nicotinic activation of cardiac vagal neurons. J Neurophysiol. 2001 Jan;85(1):164-8. doi: 10.1152/jn.2001.85.1.164. PMID: 11152716.

[5] Ryu JH, Jung HJ, Konishi S, Kim HH, Park ZY, Kim JI. Structure-activity relationships of ω-Agatoxin IVA in lipid membranes. Biochem Biophys Res Commun. 2017 Jan 1;482(1):170-175. doi: 10.1016/j.bbrc.2016.11.025. Epub 2016 Nov 9. PMID: 27838299.

[6] Singh M, Sapkota K, Sakimura K, Kano M, Cowell RM, Overstreet-Wadiche L, Hablitz JJ, Nakazawa K. Maturation of GABAergic Synaptic Transmission From Neocortical Parvalbumin Interneurons Involves N-methyl-D-aspartate Receptor Recruitment of Cav2.1 Channels. Neuroscience. 2023 Mar 1;513:38-53. doi: 10.1016/j.neuroscience.2023.01.007. Epub 2023 Jan 20. PMID: 36682446.

[7] Inan SY, Yildirim S, Tanriover G, Ilhan B. P/Q type (Cav2.1) Calcium Channel Blocker ω-Agatoxin IVA Alters Cleaved Caspase-3 and BDNF Expressions in the Rat Brain and Suppresses Seizure Activity. Mol Neurobiol. 2024 Apr;61(4):1861-1872. doi: 10.1007/s12035-023-03678-0. Epub 2023 Oct 6. PMID: 37798599.

[8] Li Z, Cong Y, Wu T, Wang T, Lou X, Yang X, Yan N. Structural basis for different ω-agatoxin IVA sensitivities of the P-type and Q-type Cav2.1 channels. Cell Res. 2024 Jun;34(6):455-457. doi: 10.1038/s41422-024-00940-5. Epub 2024 Mar 5. PMID: 38443561; PMCID: PMC11143261.