Phorbol 12-myristate 13-acetate enhances long-term potentiation in the hippocampus through activation of protein kinase cδ and εe

Eung Chang Kim, Myeong Jong Lee, Sang Yep Shin, Geun Hee Seol, Seung Ho Han, Jaeyong Yee, Chan Kim, Sun Seek Min

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Many intracellular proteins and signaling cascades contribute to the sensitivity of N-methyl-Daspartate receptors (NMDARs). One such putative contributor is the serine/threonine kinase, protein kinase C (PKC). Activation of PKC by phorbol 12-myristate 13-acetate (PMA) causes activation of extracellular signal-regulated kinase (ERK) and promotes the formation of new spines in cultured hippocampal neurons. The purpose of this study was to examine which PKC isoforms are responsible for the PMA-induced augmentation of long-term potentiation (LTP) in the CA1 stratum radiatum of the hippocampus in vitro and verify that this facilitation requires NMDAR activation. We found that PMA enhanced the induction of LTP by a single episode of theta-burst stimulation in a concentrationdependent manner without affecting to magnitude of baseline field excitatory postsynaptic potentials. Facilitation of LTP by PMA (200 nM) was blocked by the nonspecific PKC inhibitor, Ro 31-8220 (10μM); the selective PKCdelta; inhibitor, rottlerin (1μM); and the PKCe inhibitor, TAT-εV1-2 peptide (500 nM). Moreover, the NMDAR blocker DL-APV (50μM) prevented enhancement of LTP by PMA. Our results suggest that PMA contributes to synaptic plasticity in the nervous system via activation of PKCd and/or PKCε , and confirm that NMDAR activity is required for this effect.

Original languageEnglish
Pages (from-to)51-56
Number of pages6
JournalKorean Journal of Physiology and Pharmacology
Volume17
Issue number1
DOIs
Publication statusPublished - 2013 Jan

Keywords

  • Hippocampus
  • Long-term potentiation (LTP)
  • Phorbol 12-myristate 13-acetate
  • Protein kinase C (PKC)
  • Synaptic plasticity

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

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