Substance P mobilizes intracellular calcium and activates a nonselective cation conductance in rat spiral ganglion neurons

Eur J Neurosci. 2002 Dec;16(11):2095-102. doi: 10.1046/j.1460-9568.2002.02292.x.


We demonstrate the expression of functional tachykinin receptors in rat spiral ganglion neurons (SGNs) using calcium signal measurement and whole-cell patch clamp recording. Substance P (SP; 10 microm, 1 s application) induced a transient increase in intracellular calcium. The SP dose-response study showed an EC50 of 18.8 microm and a Hill slope of 0.77. Comparison between specific agonists for the three tachykinin receptor (NKR) types showed the potency NKR3 > NKR1 > NKR2 at 10 microm. The Ca2+ response could be evoked in Ca2+-free medium and was blocked by N-ethylmaleimide and U-73122, indicating that Ca2+ was released from intracellular stores via a G-protein and phospholipase C pathway. Under whole-cell voltage clamp recording at a holding potential of -50 mV, SP (10 microm, 1 s) evoked a slowly developing transient inward current. The current reversed near to 0 mV and ionic permeability experiments revealed a cation nonselective conductance also permeable to large organic cations such as N-methyl-D-glucamine and tetraethylammonium. Neither removing extracellular calcium nor chelating intracellular calcium with 10 mm BAPTA could block the SP-evoked current. This conductance appeared coupled to G-protein activation as intracellular GDP-betaS blocked the SP-evoked current. Mutual desensitization and occlusion studies with acetylcholine and ATP showed that the SP-evoked conductance share effector channels and/or intracellular processes with the purinergic/cholinergic conductance. In SGNs, SP could have both a trophic action, via a calcium response, and a neuromodulatory role, by a depolarizing action through the activation of nonselective cation channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholine / pharmacology
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Animals, Newborn
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Cation Transport Proteins / drug effects
  • Cation Transport Proteins / metabolism*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Enzyme Inhibitors / pharmacology
  • GTP-Binding Proteins / drug effects
  • GTP-Binding Proteins / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons, Afferent / cytology
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism*
  • Protein Synthesis Inhibitors / pharmacology
  • Rats
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Spiral Ganglion / cytology
  • Spiral Ganglion / drug effects
  • Spiral Ganglion / metabolism*
  • Substance P / metabolism*
  • Substance P / pharmacology
  • Type C Phospholipases / drug effects
  • Type C Phospholipases / metabolism


  • Cation Transport Proteins
  • Chelating Agents
  • Enzyme Inhibitors
  • Protein Synthesis Inhibitors
  • Substance P
  • Adenosine Triphosphate
  • Type C Phospholipases
  • GTP-Binding Proteins
  • Acetylcholine
  • Calcium