The critical role of voltage-dependent calcium channel in axonal repair following mechanical trauma

A. Nehrt, R. Rodgers, S. Shapiro, R. Borgens, R. Shi

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Membrane disruption following mechanical injury likely plays a critical role in the pathology of spinal cord trauma. It is known that intracellular calcium is a key factor that is essential to membrane resealing. However, the differential role of calcium influx through the injury site and through voltage dependent calcium channels (VDCC) has not been examined in detail. Using a well-established ex vivo guinea-pig spinal cord white matter preparation, we have found that axonal membrane resealing was significantly inhibited following transection or compression in the presence of cadmium, a non-specific calcium channel blocker, or nimodipine, a specific L-type calcium channel blocker. Membrane resealing was assessed by the changes of membrane potential and compound action potential (CAP), and exclusion of horseradish peroxidase 60 min following trauma. Furthermore, 1 μM BayK 8644, a VDCC agonist, significantly enhanced membrane resealing. Interestingly, this effect was completely abolished when the concentration of BayK 8644 was increased to 30 μM. These data suggest that VDCC play a critical role in membrane resealing. Further, there is likely an appropriate range of calcium influx through VDCC which ensures effective axonal membrane resealing. Since elevated intracellular calcium has also been linked to axonal deterioration, blockage of VDCC is proposed to be a clinical treatment for various injuries. The knowledge gained in this study will likely help us better understand the role of calcium in various CNS trauma, which is critical for designing new approaches or perhaps optimizing the effectiveness of existing methods in the treatment of CNS trauma.

Original languageEnglish (US)
Pages (from-to)1504-1512
Number of pages9
JournalNeuroscience
Volume146
Issue number4
DOIs
StatePublished - Jun 8 2007

Keywords

  • axon
  • guinea pig
  • membrane depolarization
  • membrane integrity
  • neurotrauma
  • resealing

ASJC Scopus subject areas

  • Neuroscience(all)

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