Differential downregulation of protein kinase C isoforms in spreading depression

Osten, P., Hrabetova, S., Sacktor, T. C. (1996) Differential downregulation of protein kinase C isoforms in spreading depression. Neuroscience Letters, 221 (1). pp. 37-40. ISSN 03043940 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/9014175
DOI: 10.1016/s0304-3940(96)13280-8

Abstract

Spreading depression (SD) is a propagating depolarization of populations of neurons induced by intense electrical, chemical, or mechanical stimulation, which has been proposed to be an important mechanism in the aura of migraine. SD is characterized by a transient loss of synaptic transmission and thus may involve signal transduction mechanisms known to modulate synaptic strength. To examine the underlying pathophysiological molecular mechanisms of SD, we analyzed the regulation of eight protein kinase C (PKC) isoforms by immunoblot during SD induced by a high-intensity stimulus of synaptic afferents in the CA1 region of hippocampal slices. We observed a downregulation of the conventional (α, βI, βII, γ) and the novel (δ, ε, η) PKC isoforms in SD, but no change in the atypical isozyme (ζ). The coordinate downregulation of multiple PKC isoforms may be important in the functional depression of neuronal activity in SD. In contrast, the atypical ζ, and its constitutively active fragment PKMζ, is a specific PKC isozyme that has been implicated in the maintenance of long-term potentiation (LTP) and long-term depression (LTD), widely studied models for the mechanism of memory. The stability of PKCζ and PKMζ in SD indicates that a molecular mechanism for the maintenance of LTP/LTD is relatively resistant to alterations that occur during pathophysiologically large ionic fluxes. This result could help to explain the retention of information stored in the cortex despite the massive release of excitatory neurotransmitter and neuronal depolarization that may occur during the migrainous aura.

Item Type: Paper
Uncontrolled Keywords: migraine aura protein kinase C zeta isoform spreading depression isoenzyme protein kinase c adolescent animal tissue article brain slice controlled study electrophysiology hippocampus long term potentiation migraine nonhuman priority journal rat spreading cortical depression Animals Blotting, Western Electric Stimulation Isoenzymes Long-Term Potentiation Organ Culture Techniques Rats Rats, Sprague-Dawley
Subjects: diseases & disorders
diseases & disorders > mental disorders
diseases & disorders > mental disorders > mood disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
diseases & disorders > mental disorders > mood disorders > depression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
CSHL Authors:
Communities: CSHL labs > Osten lab
Depositing User: Matt Covey
Date: 1996
Date Deposited: 04 Apr 2013 21:09
Last Modified: 04 Apr 2013 21:09
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28092

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