Restoration of TEA-induced calcium responses in fibroblasts from Alzheimer's disease patients by a PKC activator

Seetha Bhagavan, Dolores Ibarreta, Dawei Ma, Alan P. Kozikowski, René Etcheberrigaray

Research output: Contribution to journalArticlepeer-review

Abstract

Several alterations in fibroblasts of Alzheimer's disease (AD) patients have been described, including alterations in calcium regulation, protein kinase C (PKC), and potassium (K+) channels. Studies have also found reduced levels of the α isoform of PKC in brains and fibroblasts of AD patients. Since PKC is known to regulate ion channels, we studied K+ channel activity in fibroblasts from AD patients in the presence of (2S, 5S)-8-(1- decynyl)benzolactam (BL), a novel activator of PKC with improved selectivity for the α, β, and γ isoforms. We present evidence for restoration of normal K+ channel function, as measured by TEA-induced [Ca2+](i) elevations, due to activation of PKC by BL. Representative patch-clamp data further substantiate the effect of BL on restoration of 113pS K+ channel activity. Immunoblotting analyses using an α-isozyme-specific PKC antibody confirm that BL-treated fibroblasts of AD patients show increased PKC activation. The present study suggests that PKC activator-based restoration of K+ channels may offer another approach to the investigation of AD pathophysiology, which in turn could lead to the development of a useful model for AD therapeutics.

Original languageEnglish (US)
Pages (from-to)177-187
Number of pages11
JournalNeurobiology of Disease
Volume5
Issue number3
DOIs
StatePublished - Sep 1998

Keywords

  • Alzheimer's disease
  • Calcium
  • Fibroblast
  • Protein kinase C
  • TEA

ASJC Scopus subject areas

  • Neurology

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