Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|Vrt||ICC, IP, WB||Rb||Purified||Polyclonal Antibody|
|Presentation||Purified in PBS with 0.05% NaN3 and 30% Glycerol|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||Maintain at -20°C in undiluted aliquots for up to 1 year after date of receipt.|
|Material Size||200 µg|
|Reference overview||Application||Pub Med ID|
|Sodium channelopathy induced by mild axonal trauma worsens outcome after a repeat injury.|
Yuen, TJ; Browne, KD; Iwata, A; Smith, DH
Journal of neuroscience research 87 3620-5 2009
There is great concern that one mild traumatic brain injury (mTBI) predisposes individuals to an exacerbated response with a subsequent mTBI. Although no mechanism has been identified, mounting evidence suggests traumatic axonal injury (TAI) plays a role in this process. By using a cell culture system, a threshold of mild TAI was found where dynamic stretch of cortical axons at strains lower than 5% induced no overt pathological changes. However, the axons were found to display an increased expression of sodium channels (NaChs) by 24 hr. After a second, identical mild injury, pathologic increases in [Ca(2+)](i) were observed, leading to axon degeneration. The central role of NaChs in this response was demonstrated by blocking NaChs with tetrodotoxin prior to the second injury, which completely abolished postinjury increases in [Ca(2+)](i). These data suggest that mild TAI induces a form of sodium channelopathy on axons that greatly exaggerates the pathophysiologic response to subsequent mild injuries.
|Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity.|
Jie-Lin Pu,Bin Ye,Stacie L Kroboth,Elizabeth M McNally,Jonathan C Makielski,Nian-Qing Shi
Journal of molecular and cellular cardiology 44 2008
The cardiac sarcolemmal ATP-sensitive potassium channel (K(ATP)) consists of a Kir6.2 pore and an SUR2 regulatory subunit, which is an ATP-binding cassette (ABC) transporter. K(ATP) channels have been proposed to play protective roles during ischemic preconditioning. An SUR2 mutant mouse was previously generated by disrupting the first nucleotide-binding domain (NBD1), where a glibenclamide action site was located. In the mutant ventricular myocytes, a non-conventional glibenclamide-insensitive (10 microM), ATP-sensitive current (I(KATPn)) was detected in 33% of single-channel recordings with an average amplitude of 12.3+/-5.4 pA per patch, an IC(50) to ATP inhibition at 10 microM and a mean burst duration at 20.6+/-1.8 ms. Newly designed SUR2 isoform- or variant-specific antibodies identified novel SUR2 short forms in the sizes of 28 and 68 kDa in addition to a 150-kDa long form in the sarcolemmal membrane of wild-type (WT) heart. We hypothesized that channels constituted by these short forms that lack NBD1 confer I(KATPn). The absence of the long form in the mutant corresponded to loss of the conventional glibenclamide-sensitive K(ATP) currents (I(KATP)) in isolated cardiomyocytes and vascular smooth muscle cells but the SUR2 short forms remained intact. Nested exonic RT-PCR in the mutant indicated that the short forms lacked NBD1 but contained NBD2. The SUR2 short forms co-immunoprecipitated with Kir6.1 or Kir6.2 suggesting that the short forms may function as hemi-transporters reported in other eukaryotic ABC transporter subgroups. Our results indicate that different K(ATP) compositions may co-exist in cardiac sarcolemmal membrane.Full Text Article
|Traumatic axonal injury induces proteolytic cleavage of the voltage-gated sodium channels modulated by tetrodotoxin and protease inhibitors.|
Iwata, A; Stys, PK; Wolf, JA; Chen, XH; Taylor, AG; Meaney, DF; Smith, DH
The Journal of neuroscience : the official journal of the Society for Neuroscience 24 4605-13 2004
We demonstrated previously that dynamic stretch injury of cultured axons induces structural changes and Ca2+ influx modulated by tetrodotoxin (TTX)-sensitive voltage-gated sodium channels (NaChs). In the present study, we evaluated potential damage to the NaCh alpha-subunit, which can cause noninactivation of NaChs. In addition, we explored the effects of pre-injury and post-injury treatment with TTX and protease inhibition on proteolysis of the NaCh alpha-subunit and intra-axonal calcium levels ([Ca2+]i) over 60 min after trauma. After stretch injury, we found that [Ca2+]i continued to increase in untreated axons for at least 60 min. We also observed that the III-IV intra-axonal loop of the NaCh alpha-subunit was proteolyzed between 5 and 20 min after trauma. Pre-injury treatment of the axons with TTX completely abolished the posttraumatic increase in [Ca2+]i and proteolysis of the NaCh alpha-subunit. In addition, both pre-injury and post-injury inhibition of protease activity attenuated long-term increases in [Ca2+]i as well as mitigating degradation of the NaCh alpha-subunit. These results suggest a unique "feed-forward" deleterious process initiated by mechanical trauma of axons. Na+ influx through NaChs resulting from axonal deformation triggers initial increases in [Ca2+]i and subsequent proteolysis of the NaCh-subunit. In turn, degradation of the alpha-subunit promotes persistent elevations in [Ca2+]i, fueling additional pathologic changes. These observations may have important implications for developing therapeutic strategies for axonal trauma.
|Potassium channel distribution, clustering, and function in remyelinating rat axons|
Rasband, M. N., et al
J Neurosci, 18:36-47 (1998) 1998
|The clustering of axonal sodium channels during development of the peripheral nervous system|
Vabnick, I., et al
J Neurosci, 16:4914-22 (1996) 1996
|Immunocytochemical investigations of sodium channels along nodal and internodal portions of demyelinated axons|
England, J. D., et al
Microsc Res Tech, 34:445-51 (1996) 1996
|Clustering of Na+ channels and node of Ranvier formation in remyelinating axons|
Dugandzija-Novakovic, S., et al
J Neurosci, 15:492-503 (1995) 1995
|Increased numbers of sodium channels form along demyelinated axons.|
England, J D, et al.
Brain Res., 548: 334-7 (1991) 1991
Sodium channels, which are largely localized to the nodes of Ranvier in myelinated axons, appear to form new distributions along demyelinated axons. In this study a sensitive radioimmunoassay (RIA) was used to examine the changes in the total number of sodium channels that occur in nerves experimentally demyelinated in vivo with doxorubicin (adriamycin). The results clearly illustrate the development of an increased number of sodium channels during demyelination, suggesting that this process is associated with the formation of new sodium channels.
|Principal glycopeptide of the tetrodotoxin/saxitoxin binding protein from Electrophorus electricus: isolation and partial chemical and physical characterization.|
Miller, J A, et al.
Biochemistry, 22: 462-70 (1983) 1983
Preparations of the tetrodotoxin (TTX) and saxitoxin binding protein isolated from the electroplax of Electrophorus electricus are of high specific activity (greater than or equal to 2000 pmol of TTX binding sites/mg of protein) and appear to be homogeneous in that they contain only the large polypeptide previously identified to make up part of the voltage-sensitive sodium channel [Agnew, W. S., Moore, A. C., Levinson, S. R., & Raftery, M. S. (1980) Biochem. Biophys. Res. Commun. 92, 860-866]. This permits the inference that the TTX binding site, thought to be associated with the mouth of the ion channel, is located on this peptide. This peptide presumably corresponds to the large peptide, designated the alpha-peptide subunit, of the synaptosomal sodium channel [Hartshorne, R. P., & Catterall, W. A. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 4620-4624]. No convincing evidence for lower molecular weight peptides has yet been found for the electroplax protein. A rapid and convenient method is described for preparation of milligram quantities of the pure, sodium dodecyl sulfate (NaDodSO4) denatured form of the peptide, and its amino acid and carbohydrate compositions are reported. The peptide behaved anomalously on NaDodSO4-polyacrylamide gels. It was demonstrated that the molecular weight cannot be accurately quantified by this method but that the true value likely exceeds the value of 260 000 reported previously. The denatured peptide displayed an electrophoretic microheterogeneity which may be ascribed to variations in bulky carbohydrate substituents and an extremely high free mobility which is inferred to result from binding of unusually large amounts of NaDodSO4.