Phorbol 12-Myristate 13-Acetate Enhances Long-Term Potentiation in the Hippocampus through Activation of Protein Kinase Cdelta and epsilon.
10.4196/kjpp.2013.17.1.51
- Author:
Eung Chang KIM
1
;
Myeong Jong LEE
;
Sang Yep SHIN
;
Geun Hee SEOL
;
Seung Ho HAN
;
Jaeyong YEE
;
Chan KIM
;
Sun Seek MIN
Author Information
1. Department of Physiology and Biophysics, School of Medicine, Eulji University, Daejeon 301-746, Korea. ssmin@eulji.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Hippocampus;
Long-term potentiation (LTP);
Phorbol 12-myristate 13-acetate;
Protein kinase C (PKC);
Synaptic plasticity
- MeSH:
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
- From:The Korean Journal of Physiology and Pharmacology
2013;17(1):51-56
- CountryRepublic of Korea
- Language:English
-
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.
