Korean J Physiol Pharmacol.  2013 Feb;17(1):51-56. 10.4196/kjpp.2013.17.1.51.

Phorbol 12-Myristate 13-Acetate Enhances Long-Term Potentiation in the Hippocampus through Activation of Protein Kinase Cdelta and epsilon

Affiliations
  • 1Department of Physiology and Biophysics, School of Medicine, Eulji University, Daejeon 301-746, Korea. ssmin@eulji.ac.kr
  • 2Department of Anesthesiology and Pain Medicine, School of Medicine, Konkuk University, Chungju 380-701, Korea.
  • 3Department of Basic Nursing Science, School of Nursing, Korea University, Seoul 136-703, Korea.

Abstract

Many intracellular proteins and signaling cascades contribute to the sensitivity of N-methyl-D-aspartate 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 concentration-dependent 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 (10microM); the selective PKCdelta inhibitor, rottlerin (1microM); and the PKCepsilon inhibitor, TAT-epsilonV1-2 peptide (500 nM). Moreover, the NMDAR blocker DL-APV (50microM) prevented enhancement of LTP by PMA. Our results suggest that PMA contributes to synaptic plasticity in the nervous system via activation of PKCdelta and/or PKCepsilon, and confirm that NMDAR activity is required for this effect.

Keyword

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

MeSH Terms

2-Amino-5-phosphonovalerate
Acetophenones
Benzopyrans
Excitatory Postsynaptic Potentials
Hippocampus
Indoles
Long-Term Potentiation
Nervous System
Neurons
Phorbols
Phosphotransferases
Protein Isoforms
Protein Kinases
Proteins
Receptors, N-Methyl-D-Aspartate
Spine
2-Amino-5-phosphonovalerate
Acetophenones
Benzopyrans
Indoles
Phorbols
Phosphotransferases
Protein Isoforms
Protein Kinases
Proteins
Receptors, N-Methyl-D-Aspartate
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