Traumatic axonal injury induces calcium influx modulated by tetrodotoxin-sensitive sodium channels.

摘要: Diffuse axonal injury (DAI) is one of the most common and important pathologies resulting from mechanical deformation brain during trauma. It has been hypothesized that calcium influx into axons plays a major role in pathophysiology DAI. However, there little direct evidence to support this hypothesis, mechanisms potential entry have not explored. In present study, we used an vitro model stretch evaluate extent modulation after Using calcium-sensitive dye, observed dramatic increase intra-axonal levels immediately injury. Axonal calcium-free extracellular solution resulted no change concentration, suggesting source for increased post-traumatic levels. We also found was completely abolished by application sodium channel blocker tetrodotoxin or replacement withN-methyl-d-glucamine. addition, voltage-gated (VGCC) ω-conotoxin MVIIC attenuated calcium. Furthermore, blockade Na+–Ca2+ exchanger with bepridil modestly reduced contrast previously proposed trauma, through mechanically produced pores (mechanoporation). Rather, our results suggest traumatic induces abnormal sensitive Na+ channels, which subsequently triggers via opening VGCCs reversal exchanger.