Inhibition of calcineurin inhibits the desensitization of capsaicin-evoked currents in cultured dorsal root ganglion neurones from adult rats

Pflugers Arch. 1996 Apr;431(6):828-37. doi: 10.1007/s004240050074.


Capsaicin activates a non-specific cation conductance in mammalian sensory neurones. If capsaicin is applied continuously or repeatedly then there is a progressive decline in responsiveness. We have studied the mechanism of this desensitization using electrophysiological methods in cultured dorsal root ganglion neurones from adult rats. The rate of desensitization of capsaicin-induced responses is partly dependent on the extracellular calcium concentration and is slower when extracellular calcium is reduced. Desensitization is strongly inhibited by intracellular application of the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N, N, N',N'-tetraacetic acid (BAPTA). These data suggest that desensitization is due to a rapid rise in intracellular calcium levels which occurs when capsaicin-sensitive ion channels are activated. Desensitization is not reduced by the non-specific protein kinase inhibitors H7 or staurosporine or by okadaic acid, a selective inhibitor of protein phosphatases 1 and 2A. Desensitization is greatly reduced by cyclosporin A complexed to cyclophilin, which is a specific inhibitor of protein phoshatase 2B (calcineurin). A mechanism for desensitization of capsaicin responsiveness is proposed whereby the evoked rise in calcium activates calcineurin leading to dephosphorylation and desensitization of the capsaicin-sensitive ion channels.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcineurin
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calmodulin-Binding Proteins / antagonists & inhibitors*
  • Calmodulin-Binding Proteins / physiology
  • Capsaicin / pharmacology*
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Cyclosporine / pharmacology
  • Drug Resistance
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Evoked Potentials / drug effects*
  • Evoked Potentials / physiology
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / physiology*
  • Ion Channel Gating
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Ligands
  • Phosphoprotein Phosphatases / antagonists & inhibitors*
  • Phosphoprotein Phosphatases / physiology
  • Phosphorylation
  • Protein Kinase Inhibitors
  • Rats


  • Calmodulin-Binding Proteins
  • Chelating Agents
  • Enzyme Inhibitors
  • Ion Channels
  • Ligands
  • Protein Kinase Inhibitors
  • Egtazic Acid
  • Cyclosporine
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Adenosine Triphosphate
  • Calcineurin
  • Phosphoprotein Phosphatases
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Capsaicin
  • Calcium