Protein kinase C-mediated inhibition of an inward rectifier potassium channel by substance P in nucleus basalis neurons.
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.
Takano
K
K
Department of Anatomy and Cell Biology, University of Illinois at Chicago, College of Medicine 60612, USA.
Stanfield
P R
PR
Nakajima
S
S
Nakajima
Y
Y
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004988:Ethers, Cyclic / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D019311:Staurosporine; D013373:Substance P / Q000494:pharmacology*; D013377:Substantia Innominata / Q000502:physiology*
D000470:Alkaloids; D004988:Ethers, Cyclic; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019319:Okadaic Acid; D013373:Substance P; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D019311:Staurosporine