The role of calcium in capsaicin-induced desensitization in rat cultured dorsal root ganglion neurons

Neuroscience. 1993 Aug;55(4):1015-23. doi: 10.1016/0306-4522(93)90315-7.


The effects of capsaicin cytosolic Ca2+ concentration ([Ca2+]i) were measured in individual dorsal root ganglion neurons of the rat in culture. Capsaicin produced a rapid concentration-dependent (EC50 value of 72 nM) increase in [Ca2+]i which was entirely dependent on Ca2+ entry. Exposure of the neurons to a high concentration of capsaicin resulted in desensitization, but only in the presence of external Ca2+. Raising [Ca2+]i with a depolarizing concentration of potassium or the Ca2+ ionophore ionomycin did not reduce the response to a subsequent application of capsaicin. Capsaicin did not induce desensitization in Ca(2+)-free medium even if [Ca2+]i was simultaneously raised with a combination of ionomycin plus carbonyl cyanide m-chlorophenyl-hydrazone. Okadaic acid, a known inhibitor of protein phosphatases 1 and 2A, caused a transient dose-dependent (EC50 value, 100nM) rise in [Ca2+]i, but had no effect on either the responsiveness to capsaicin or capsaicin induced desensitization. The capsaicin antagonist capsazepine blocked the increase in [Ca2+]i evoked by capsaicin and prevented desensitization. These results suggest that desensitization requires the presence of extracellular Ca2+, cannot be mimicked by raising the concentration of [Ca2+]i and may involve Ca2+ entry through activated capsaicin-operated ion channels.

MeSH terms

  • Animals
  • Bradykinin / pharmacology
  • Calcium / pharmacology
  • Calcium / physiology*
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology*
  • Cells, Cultured
  • Drug Tolerance
  • Ethers, Cyclic / pharmacology
  • Extracellular Space / metabolism
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects*
  • Inositol Phosphates / metabolism
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Ionomycin / pharmacology
  • Mitochondria / metabolism
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / physiology
  • Okadaic Acid
  • Potassium Chloride / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects


  • Ethers, Cyclic
  • Inositol Phosphates
  • Ion Channels
  • Okadaic Acid
  • Ionomycin
  • Potassium Chloride
  • capsazepine
  • Capsaicin
  • Bradykinin
  • Calcium