Journal article
Calpain Mediates Proteolysis of the Voltage-Gated Sodium Channel alpha-Subunit
The Journal of neuroscience, v 29(33), pp 10350-10356
19 Aug 2009
PMID: 19692609
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Alterations in the expression, molecular composition, and localization of voltage-gated sodium channels play major roles in a broad range of neurological disorders. Recent evidence identifies sodium channel proteolysis as a key early event after ischemia and traumatic brain injury, further expanding the role of the sodium channel in neurological diseases. In this study, we investigate the protease responsible for proteolytic cleavage of voltage-gated sodium channels (NaChs). NaCh proteolysis occurs after protease activation in rat brain homogenates, pharmacological disruption of ionic homeostasis in cortical cultures, and mechanical injury using an in vitro model of traumatic brain injury. Proteolysis requires Ca2+ and calpain activation but is not influenced by caspase-3 or cathepsin inhibition. Proteolysis results in loss of the full-length alpha-subunits, and the creation of fragments comprising all domains of the channel that retain interaction even after proteolysis. Cell surface biotinylation after mechanical injury indicates that proteolyzed NaChs remain in the membrane before noticeable evidence of neuronal death, providing a mechanism for altered action potential initiation, propagation, and downstream signaling events after Ca2+ elevation.
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Details
- Title
- Calpain Mediates Proteolysis of the Voltage-Gated Sodium Channel alpha-Subunit
- Creators
- Catherine R. von Reyn - University of PennsylvaniaJennifer M. Spaethling - University of PennsylvaniaMahlet N. Mesfin - University of PennsylvaniaMarek Ma - University of PennsylvaniaRobert W. Neumar - University of PennsylvaniaDouglas H. Smith - University of PennsylvaniaRobert Siman - University of PennsylvaniaDavid F. Meaney - University of Pennsylvania
- Publication Details
- The Journal of neuroscience, v 29(33), pp 10350-10356
- Publisher
- Soc Neuroscience
- Number of pages
- 7
- Grant note
- R01HD041699 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) University of Pennsylvania Preclinical Vector Core facility NS 35712; NS PPG P01 NS 056202; U24NS050606 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA NHBLI Gene Therapy Resource Program R01NS048234 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000269087300018
- Scopus ID
- 2-s2.0-69049116237
- Other Identifier
- 991019186664804721
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- Web of Science research areas
- Neurosciences