Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|R, M||WB, IHC||Rb||Affinity Purified||Polyclonal Antibody|
|Description||Anti-Sodium Channel Antibody, Voltage Gated, Brain Type I|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||Maintain lyophilized material at -20°C for up to 12 months. After reconstitution maintain at -20°C in undiluted aliquots for up to 6 months. Avoid repeated freeze/thaw cycles.|
|Material Size||200 µL|
|RABBIT ANTI-BRAIN TYPE I VOLTAGE GATED SODIUM CHANNEL AFFINITY PURIFIED POLYCLONAL ANTIBODY - 2154059||2154059|
|RABBIT ANTI-BRAIN TYPE I VOLTAGE GATED SODIUM CHANNEL AFFINITY PURIFIED POLYCLONAL ANTIBODY - 2397061||2397061|
|RABBIT ANTI-BRAIN TYPE I VOLTAGE GATED SODIUM CHANNEL AFFINITY PURIFIED POLYCLONAL ANTIBODY - 2055427||2055427|
|RABBIT ANTI-BRAIN TYPE I VOLTAGE GATED SODIUM CHANNEL AFFINITY PURIFIED POLYCLONAL ANTIBODY - 2318080||2318080|
|Reference overview||Pub Med ID|
|Spontaneous epileptiform discharges in a mouse model of Alzheimer\'s disease are suppressed by antiepileptic drugs that block sodium channels. |
Ziyatdinova S, Gurevicius K, Kutchiashvili N, Bolkvadze T, Nissinen J, Tanila H, Pitkänen A
Epilepsy research 94 75-85. 2011
Previous studies have demonstrated an increased risk of epilepsy in patients with Alzheimer\'s disease (AD). Also, in many mouse models of AD, animals have spontaneous seizures and frequent epileptiform discharges (EDs). Abnormal function of sodium channels has been proposed to contribute to hyperexcitability in a manner suggesting that drugs that block sodium channels might exacerbate the condition. Here we addressed this question by investigating whether common antiepileptic drugs (AEDs) that block sodium channels, including carbamazepine (CBZ), phenytoin (DPH), or valproic acid (VPA) have any effect on spontaneous seizures or EDs in APdE9 mice. Mice were successively treated with vehicle, followed by CBZ (10mg/kg, t.i.d.), DPH (10mg/kg, t.i.d.), or VPA (260 mg/kg, b.i.d.) for 3d. After wash-out and new vehicle treatment, higher doses of CBZ (40 mg/kg, t.i.d.), DPH (40 mg/kg, t.i.d.), or VPA (400mg/kg, b.i.d.) were administered for 3d (DPH) or 5d (CBZ, VPA). During the entire experiment, mice were under continuous (24/7) video-EEG monitoring. Our data show that each treatment reduced the number of spontaneous electrographic EDs. VPA was the most effective by reducing the ED frequency below 50% of that at baseline in 75% of mice. Western blot analysis of the Na(v)1.1 protein levels in the ventral temporal cortex and the hippocampus did not reveal any differences between the genotypes. Under the conditions tested, sodium channel blocking AEDs suppressed epileptiform activity in APdE9 mice with increased amyloid pathology. Whether this applies to other mouse models of AD with different APP mutations and/or genetic background remains to be explored.Copyright © 2011 Elsevier B.V. All rights reserved.
|Persistent Nav1.6 current at axon initial segments tunes spike timing of cerebellar granule cells. |
Nancy Osorio,Laurence Cathala,Miriam H Meisler,Marcel Crest,Jacopo Magistretti,Patrick Delmas
The Journal of physiology 588 2010
Cerebellar granule (CG) cells generate high-frequency action potentials that have been proposed to depend on the unique properties of their voltage-gated ion channels. To address the in vivo function of Nav1.6 channels in developing and mature CG cells, we combined the study of the developmental expression of Nav subunits with recording of acute cerebellar slices from young and adult granule-specific Scn8a KO mice. Nav1.2 accumulated rapidly at early-formed axon initial segments (AISs). In contrast, Nav1.6 was absent at early postnatal stages but accumulated at AISs of CG cells from P21 to P40. By P40-P65, both Nav1.6 and Nav1.2 co-localized at CG cell AISs. By comparing Na(+) currents in mature CG cells (P66-P74) from wild-type and CG-specific Scn8a KO mice, we found that transient and resurgent Na(+) currents were not modified in the absence of Nav1.6 whereas persistent Na(+) current was strongly reduced. Action potentials in conditional Scn8a KO CG cells showed no alteration in threshold and overshoot, but had a faster repolarization phase and larger post-spike hyperpolarization. In addition, although Scn8a KO CG cells kept their ability to fire action potentials at very high frequency, they displayed increased interspike-interval variability and firing irregularity in response to sustained depolarization. We conclude that Nav1.6 channels at axon initial segments contribute to persistent Na(+) current and ensure a high degree of temporal precision in repetitive firing of CG cells.Full Text Article
|A missense mutation of the gene encoding voltage-dependent sodium channel (Nav1.1) confers susceptibility to febrile seizures in rats. |
Mashimo T, Ohmori I, Ouchida M, Ohno Y, Tsurumi T, Miki T, Wakamori M, Ishihara S, Yoshida T, Takizawa A, Kato M, Hirabayashi M, Sasa M, Mori Y, Serikawa T
J Neurosci 30 5744-53. 2010
Although febrile seizures (FSs) are the most common convulsive syndrome in infants and childhood, the etiology of FSs has remained unclarified. Several missense mutations of the Na(v)1.1 channel (SCN1A), which alter channel properties, have been reported in a familial syndrome of GEFS+ (generalized epilepsy with febrile seizures plus). Here, we generated Scn1a-targeted rats carrying a missense mutation (N1417H) in the third pore region of the sodium channel by gene-driven ENU (N-ethyl-N-nitrosourea) mutagenesis. Despite their normal appearance under ordinary circumstances, Scn1a mutant rats exhibited remarkably high susceptibility to hyperthermia-induced seizures, which involve generalized clonic and/or tonic-clonic convulsions with paroxysmal epileptiform discharges. Whole-cell patch-clamp recordings from HEK cells expressing N1417H mutant channels and from hippocampal GABAergic interneurons of N1417H mutant rats revealed a significant shift of the inactivation curve in the hyperpolarizing direction. In addition, clamp recordings clearly showed the reduction in action potential amplitude in the hippocampal interneurons of these rats. These findings suggest that a missense mutation (N1417H) of the Na(v)1.1 channel confers susceptibility to FS and the impaired biophysical properties of inhibitory GABAergic neurons underlie one of the mechanisms of FS.
|Distinct subcellular localization of different sodium channel alpha and beta subunits in single ventricular myocytes from mouse heart |
Maier, Sebastian K G, et al
Circulation, 109:1421-7 (2004) 2004
|Neuronal death and perinatal lethality in voltage-gated sodium channel alpha(II)-deficient mice. |
Planells-Cases, R, et al.
Biophys. J., 78: 2878-91 (2000) 2000
Neural activity is crucial for cell survival and fine patterning of neuronal connectivity during neurodevelopment. To investigate the role in vivo of sodium channels (NaCh) in these processes, we generated knockout mice deficient in brain NaChalpha(II). NaChalpha(II)(-/-) mice were morphologically and organogenically indistinguishable from their NaChalpha(+/-) littermates. Notwithstanding, NaChalpha(II)(-/-) mice died perinatally with severe hypoxia and massive neuronal apoptosis, notably in the brainstem. Sodium channel currents recorded from cultured neurons of NaChalpha(II)(-/-) mice were sharply attenuated. Death appears to arise from severe hypoxia consequent to the brainstem deficiency of NaChalpha(II). NaChalpha(II) expression is, therefore, redundant for embryonic development but essential for postnatal survival.
|AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing. |
Zhou, D, et al.
J. Cell Biol., 143: 1295-304 (1998) 1998
Voltage-gated sodium channels (NaCh) are colocalized with isoforms of the membrane-skeletal protein ankyrinG at axon initial segments, nodes of Ranvier, and postsynaptic folds of the mammalian neuromuscular junction. The role of ankyrinG in directing NaCh localization to axon initial segments was evaluated by region-specific knockout of ankyrinG in the mouse cerebellum. Mutant mice exhibited a progressive ataxia beginning around postnatal day P16 and subsequent loss of Purkinje neurons. In mutant mouse cerebella, NaCh were absent from axon initial segments of granule cell neurons, and Purkinje cells showed deficiencies in their ability to initiate action potentials and support rapid, repetitive firing. Neurofascin, a member of the L1CAM family of ankyrin-binding cell adhesion molecules, also exhibited impaired localization to initial segments of Purkinje cell neurons. These results demonstrate that ankyrinG is essential for clustering NaCh and neurofascin at axon initial segments and is required for physiological levels of sodium channel activity.
|RABBIT ANTI-BRAIN TYPE I VOLTAGE GATED SODIUM CHANNEL AFFINITY PURIFIED POLYCLONAL ANTIBODY|