Nav1.1
NaV1.1, encoded by SCN1A, supports neuronal action-potential signaling and is closely linked to epilepsy biology[1]. Mechanistically, NaV1.1 localizes to axons of parvalbumin-positive inhibitory interneurons, positioning this channel within GABAergic circuit control[2]. In Dravet syndrome models, Scn1a dysfunction reduces sodium current in GABAergic interneurons, weakens inhibitory output, and promotes seizure susceptibility[3][4][5]. Compared with NaV1.6, NaV1.1 represents the inhibitory side of neuronal excitation-inhibition balance, whereas NaV1.6 overactivity supports excitatory epileptic mechanisms[6]. For experimental applications, selective NaV1.1 activation with Hm1a restored inhibitory interneuron function and reduced seizures in Dravet syndrome mice, while small-molecule NaV1.1 activators increased fast-spiking interneuron excitability and GABAergic transmission[7][8].
References:
- [1]. Catterall WA, et al. NaV1.1 channels and epilepsy. J Physiol. 2010 Jun 1;588(Pt 11):1849-59. [Content Brief]
- [2]. Ogiwara I, et al. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J Neurosci. 2007 May 30;27(22):5903-14. [Content Brief]
- [3]. Yu FH, et al. Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat Neurosci. 2006 Sep;9(9):1142-9. [Content Brief]
- [4]. Cheah CS, et al. Specific deletion of NaV1.1 sodium channels in inhibitory interneurons causes seizures and premature death in a mouse model of Dravet syndrome. Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14646-51. [Content Brief]
- [5]. Tai C, et al. Impaired excitability of somatostatin- and parvalbumin-expressing cortical interneurons in a mouse model of Dravet syndrome. Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):E3139-48. [Content Brief]
- [6]. Weuring WJ, et al. NaV1.1 and NaV1.6 selective compounds reduce the behavior phenotype and epileptiform activity in a novel zebrafish model for Dravet Syndrome. PLoS One. 2020 Mar 5;15(3):e0219106. [Content Brief]
- [7]. Richards KL, et al. Selective NaV 1.1 activation rescues Dravet syndrome mice from seizures and premature death. Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):E8077-E8085. [Content Brief]
- [8]. Chow CY, et al. A selective NaV 1.1 activator with potential for treatment of Dravet syndrome epilepsy. Biochem Pharmacol. 2020 Nov;181:113991. [Content Brief]
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Nav1.1 Related Products (11)
Related Products (11)
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ICA-121431
0 ImagesICA-121431 is a nanomolar potent and broad-spectrum voltage-gated sodium channel (Nav) blocker, shows equipotent selectivity for human Nav1.1 and Nav1.3 subtypes with IC50 values of 13 nM and 23 nM, respectively. ICA-121431 shows less potent inhibition of Nav1.2 (IC50=240 nM) and 1,000 fold selectivity against Nav1.4, Nav1.6, and the TTX-resistant human Nav1.5 and Nav1.8 channels (IC50s >10 μM).
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PF-06456384 trihydrochloride
0 ImagesPF-06456384 trihydrochloride is an extremely potent and selective Nav1.7 sodium channel blocker (IC50: 0.01 nM for hNaV1.7; 75 nM for rNaV1.7; <0.1 nM for mNaV1.7). PF-06456384 trihydrochloride shows no significant analgesic efficacy in the mouse Formalin pain model.
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GDC-0310
0 ImagesGDC-0310 is a selective acyl-sulfonamide Nav1.7 inhibitor, with an IC50 of 0.6 nM for hNav1.7.
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AA43279
0 ImagesAA43279 is an in gamma-aminobutyric acid (GABA) fast-firing interneurons located activator for Nav1.1 channel (SCN1A) with an EC50 of 9.5 μM. AA43279 enhances specific neuronal firing activity in vitro, and exhibits anticonvulsant activity in rat MEST model.
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Phrixotoxin 3
0 ImagesCat. No.: HY-P1218CAS No.: 880886-00-0Phrixotoxin 3 is a potent blocker of voltage-gated sodium channels, with IC50s of 0.6, 42, 72, 288, 610 nM for NaV1.2, NaV1.3, NaV1.4, NaV1.1 and NaV1.5, respectively. Phrixotoxin 3 modulates voltage-gated sodium channels with properties similar to those of typical gating-modifier toxins, both by causing a depolarizing shift in gating kinetics and by blocking the inward component of the sodium current.
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Hm1a
0 ImagesCat. No.: HY-P5183Hm1a is a venom peptide and a selective hNaV1.1 activator with an EC50 of 7.5 nM. Hm1a enhances hNaV1.1 and hNaV1.3 channel currents via delayed inactivation. Hm1a restores action potential firing in Dravet syndrome GABAergic inhibitory interneurons, reduces interictal epileptiform discharges and whole-brain hyperexcitability, lowers seizure frequency, and rescues premature death in Dravet syndrome mice. Hm1a can be used for the research of neurological disease, such as Dravet syndrome.
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Ceratotoxin-1
0 ImagesCat. No.: HY-P5811Synonyms: CcoTx1; β-TRTX-cm1aCeratotoxin-1 (CcoTx1), a peptide toxin, is an voltage-gated sodium channel subtypes inhibitor. Ceratotoxin-1 inhibits Nav1.1/β1, Nav1.2/β1, Nav1.4/β1, and Nav1.5/β1 with IC50 of 523 nM, 3 nM, 888 nM, and 323 nM, respectively. Ceratotoxin-1 also inhibits Nav1.8/β1.
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GTx1-15
0 ImagesCat. No.: HY-P5793GTx1-15 is an inhibitor cystine knot (ICK) peptide that inhibits the voltage-dependent calcium channel Cav3.1 and the voltage-dependent sodium channels Nav1.3 and Nav1.7.
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Zorevunersen
0 ImagesSynonyms: STK-001Zorevunersen is an antisense oligonucleotide targeting the Scn1a gene based on TANGO technology. Zorevunersen increases Scn1a mRNA transcripts and elevates the expression level of NaV1.1 protein. Zorevunersen restores the excitability of PV interneurons, thereby reducing seizures and prolonging survival in mice. Zorevunersen can be used for research on Dravet syndrome.
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