Nav1.4
NaV1.4 is highly expressed in skeletal muscle, where it carries almost all inward Na+ current that generates the muscle action potential[1]. Mechanistically, the human NaV1.4-β1 structure defines the pore domain, voltage-sensing domains, and β1 subunit, supporting research on Na+ permeation, fast inactivation, and drug discovery for NaV channelopathies[2]. In skeletal muscle disease models, SCN4A/NaV1.4 mutations alter excitability through gain or loss of function, producing myotonia, weakness, periodic paralysis, congenital myopathy, or fetal hypokinesia[3][4]. Compared with related sodium-channel isoforms, NaV1.4 is the specific skeletal muscle sodium channel isoform, while NaV1.5 can be transiently re-expressed after denervation[5]. For experimental applications, µ-conotoxins differentially block NaV1.1-1.8 channels, and ranolazine blocks human NaV1.4 channels and paramyotonia congenita mutants[6][7].
Références:
- [1]. Cannon SC. Sodium Channelopathies of Skeletal Muscle. Handb Exp Pharmacol. 2018;246:309-330. doi: 10.1007/164_2017_52. PMID: 28939973; PMCID: PMC5866235. et al. Sodium Channelopathies of Skeletal Muscle. Handb Exp Pharmacol. 2018;246:309-330. [Content Brief]
- [2]. Pan X, et al. Structure of the human voltage-gated sodium channel Nav 1.4 in complex with β1. Science. 2018 Oct 19;362(6412):eaau2486. [Content Brief]
- [3]. Jurkat-Rott K, et al. Sodium channelopathies of skeletal muscle result from gain or loss of function. Pflugers Arch. 2010 Jul;460(2):239-48. [Content Brief]
- [4]. Zaharieva IT, et al. Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy. Brain. 2016 Mar;139(Pt 3):674-91. [Content Brief]
- [5]. De Bellis M, et al. Blockers of Skeletal Muscle Nav 1.4 Channels: From Therapy of Myotonic Syndrome to Molecular Determinants of Pharmacological Action and Back. Int J Mol Sci. 2023 Jan 3;24(1):857. [Content Brief]
- [6]. Wilson MJ, et al. μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve. Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10302-7. [Content Brief]
- [7]. El-Bizri N, et al. Ranolazine block of human Na v 1.4 sodium channels and paramyotonia congenita mutants. Channels (Austin). 2011 Mar-Apr;5(2):161-72. [Content Brief]
All Product Categories
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Nav1.4 Produits associés (15)
Produits associés (15)
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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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TC-N 1752
0 ImagesTC-N 1752 is a potent and orally active inhibitor of Nav1.7, with IC50s of 0.17 μM, 0.3 μM, 0.4 μM, 1.1 μM and 2.2 μM at hNav1.7, hNav1.3, hNav1.4, hNaV1.5 and rNav1.8, respectively. TC-N 1752 also inhibits tetrodotoxin-sensitive sodium channels. TC-N 1752 shows analgesic efficacy in the Formalin model of pain.
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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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Nav1.7-IN-23
0 ImagesCat. No.: HY-189066CAS No.: 3138159-82-4Nav1.7-IN-23 is an orally active, selective NaV1.7 inhibitor. Nav1.7-IN-23 exhibits electrophysiological regulatory effects in mouse dorsal root ganglion neurons. Nav1.7-IN-23 can be used for the research of acute pain, chronic inflammatory pain and neuropathic pain.
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Huwentoxin-IV TFA
0 ImagesCat. No.: HY-P1220APureté: 99.18%Huwentoxin-IV TFA is a potent and selective sodium channel blocker, inhibits neuronal Nav1.7, Nav1.2, Nav1.3 and Nav1.4 with IC50s of 26, 150, 338 and 400 nM, respectively. Huwentoxin-IV TFA preferentially blocks peripheral nerve subtype Nav1.7 by binding neurotoxin receptor site 4. Huwentoxin-IV TFA has analgesic effects on animal models of inflammatory and neuropathic pain.
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GpTx-1 TFA
0 ImagesCat. No.: HY-P1681APureté: 99.56%GpTx-1 TFA is a peptide-based NaV1.7 sodium channel antagonist isolated from the venom of the Chilean spider Grammostola porter. GpTx-1 TFA demonstrates potent inhibitory activity against the NaV1.7 channel with an IC50 value of 10 nM, while exhibiting excellent selectivity for NaV1.4 (IC50 = 0.301 μM) and NaV1.5 (IC50 = 4.20 μM), showing >20-fold and >950-fold selectivity respectively.
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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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hERG-IN-3
0 ImagesCat. No.: HY-175289hERG-IN-3 is an orally active hERG blocker with an IC50 of 44.5 nM. hERG-IN-3 exhibits a Ki for β2-adrenergic receptor of 14 nM. hERG-IN-3 exhibits the skeletal muscle Nav1.4 and sodium channel-blocking activities (IC50 = 4.4 μM, 3-fold increasement than hNav1.5). hERG-IN-3 displays a potent antimyotonic activity in an animal model. hERG-IN-3 can be used for the study of Myotonia Congenita.
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GpTx-1
0 ImagesCat. No.: HY-P1681CAS No.: 1661050-12-9GpTx-1 is a peptide-based NaV1.7 sodium channel antagonist isolated from the venom of the Chilean spider Grammostola porter. GpTx-1 demonstrates potent inhibitory activity against the NaV1.7 channel with an IC50 value of 10 nM, while exhibiting excellent selectivity for NaV1.4 (IC50 = 0.301 μM) and NaV1.5 (IC50 = 4.20 μM), showing >20-fold and >950-fold selectivity respectively.
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Huwentoxin-IV
0 ImagesCat. No.: HY-P1220CAS No.: 526224-73-7Huwentoxin-IV is a potent and selective sodium channel blocker, inhibits neuronal Nav1.7, Nav1.2, Nav1.3 and Nav1.4 with IC50s of 26, 150, 338 and 400 nM, respectively. Huwentoxin-IV preferentially blocks peripheral nerve subtype Nav1.7 by binding neurotoxin receptor site 4. Huwentoxin-IV has analgesic effects on animal models of inflammatory and neuropathic pain.
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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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Methocarbamol-d5
0 ImagesCat. No.: HY-B0262SCAS No.: 1189699-70-4Methocarbamol-d5 is deuterium labeled Methocarbamol. Methocarbamol is an orally active central muscle relaxant and blocks muscular Nav1.4 channel.
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