The effect of down regulation of protein kinase C on the inhibitory modulation of dorsal root ganglion neuron Ca2+ currents by neuropeptide Y

D. A. Ewald, H. J G Matthies, T. M. Perney, M. W. Walker, R. J. Miller

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Dorsal root ganglion (DRG) neurons cultured from neonatal rats contained high concentrations of protein kinase C (PKC). Normally, the majority of the enzyme activity was found in the cytosol and considerably less was associated with the membrane fraction. Upon incubation with the phorbol ester phorbol dibutyrate (PDBu, 10-6 M) for 20 min, PKC activity increased in the membrane-associated fraction and decreased in the cytoplasmic fraction. Longer incubations with phorbol ester also induced a decline in membrane-associated PKC activity. If incubations were continued for periods of over 10 hr, both membrane and cytosolic PKC activity declined essentially to zero. Down-regulation of PKC had no effect on the number or affinity of 125I-neuropeptide Y (NPY) binding sites on DRG cells or on the absolute magnitude of the DRG Ca2+ current. However, the ability of NPY to inhibit the DRG Ca2+ current was greatly reduced. When sustained Ca2+ currents were evoked from depolarized holding potentials (-40mV), all concentrations of NPY (10-10-10-7 M) were less effective. In contrast, higher concentrations of NPY still blocked the transient position of the DRG Ca2+ current evoked from hyperpolarized holding potentials. These results support the suggestion that PKC is involved in the inhibitory modulation of DRG Ca2+ currents by neurotransmitters. The precise role of PKC may vary depending on the type of Ca2+ channel involved.

Original languageEnglish (US)
Pages (from-to)2447-2451
Number of pages5
JournalJournal of Neuroscience
Volume8
Issue number7
DOIs
StatePublished - 1988

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'The effect of down regulation of protein kinase C on the inhibitory modulation of dorsal root ganglion neuron Ca2+ currents by neuropeptide Y'. Together they form a unique fingerprint.

Cite this