Capsaicin-induced neurotoxicity in cultured dorsal root ganglion neurons: Involvement of calcium-activated proteases

P. S. Chard, D. Bleakman, J. R. Savidge, R. J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

We examined the mechanism by which capsaicin produces its toxic effects on cultures of rat sensory neurons. Capsaicin caused a robust increase in [Ca2+]i in a subpopulation of cultured rat dorsal root ganglion neurons. Similarly, a brief exposure to capsaicin resulted in delayed degeneration of a subpopulation of the cells. This subpopulation (about 35% of the cells present) was characterized by a capsaicin-induced uptake of Co2+, which could be detected cytochemically. Both capsaicin-induced Co2+ uptake and capsaicin-induced cell death were blocked by the capsaicin antagonist Ruthenium Red. Cell death was also prevented by removal of external calcium or by inhibiting calcium-activated proteases such as calpain. Evidence that calpain activity was increased was provided by examining the amount of degradation of the preferred calpain substrate α-spectrin. Capsaicin treatment produced a significant increase in the levels of the 150,000 molecular weight spectrin breakdown product. Furthermore, applying the protease inhibitors E64 or MDL 28,170 reduced capsaicin-mediated cell death. It is concluded that capsaicin kills a subpopulation of sensory neurons by activating a receptor-operated channel. The consequent Ca2+ ion influx causes large increases in [Ca2+]i and subsequent activation of Ca2+-sensitive proteases. This model provides support for the role of [Ca2+]i as the orchestrator of delayed neuronal degeneration.

Original languageEnglish (US)
Pages (from-to)1099-1108
Number of pages10
JournalNeuroscience
Volume65
Issue number4
DOIs
StatePublished - Apr 1995

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Capsaicin-induced neurotoxicity in cultured dorsal root ganglion neurons: Involvement of calcium-activated proteases'. Together they form a unique fingerprint.

Cite this