Protein kinase C-mediated inhibition of an inward rectifier potassium channel by substance P in nucleus basalis neurons

Neuron. 1995 May;14(5):999-1008. doi: 10.1016/0896-6273(95)90338-0.


In nucleus basalis neurons, substance P (SP) causes a slow excitation, mediated through a pertussis toxin-insensitive G protein, by suppressing an inward rectifier K+ channel. Here we report that SP applied outside the patch pipette inhibited the single-channel activity, recorded on-cell, of the inward rectifier. The PKC inhibitors staurosporine and PKC(19-36) suppressed this effect in whole-cell mode and in on-cell single-channel mode. A diacylglycerol analog mimicked the SP effect, and PKC(19-36) suppressed this analog effect. SP irreversibly suppressed the inward rectifier in neurons treated with okadaic acid. These results indicate that a diffusible messenger mediates the SP effect, that its signal transduction involves phosphorylation by PKC, and that dephosphorylation by a serine/threonine protein phosphatase mediates its recovery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaloids / pharmacology
  • Animals
  • Cells, Cultured
  • Ethers, Cyclic / pharmacology
  • Neurons / physiology*
  • Okadaic Acid
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Potassium Channel Blockers*
  • Potassium Channels / physiology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Rats
  • Signal Transduction
  • Staurosporine
  • Substance P / pharmacology*
  • Substantia Innominata / physiology*


  • Alkaloids
  • Ethers, Cyclic
  • Potassium Channel Blockers
  • Potassium Channels
  • Okadaic Acid
  • Substance P
  • Protein Kinase C
  • Phosphoprotein Phosphatases
  • Staurosporine