title: Phorbol 12-Myristate 13-Acetate Enhances Long-Term Potentiation in the Hippocampus through Activation of Protein Kinase Cδ and ε.
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 (10µM); the selective PKCδ inhibitor, rottlerin (1µM); and the PKCε 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 PKCδ and/or PKCε, and confirm that NMDAR activity is required for this effect.
authors: Department of Physiology and Biophysics, School of Medicine, Eulji University, Daejeon 301-746, Korea.
authors: Eung Chang
authors: EC
authors: Kim
authors: Myeong Jong
authors: MJ
authors: Lee
authors: Sang Yep
authors: SY
authors: Shin
authors: Geun Hee
authors: GH
authors: Seol
authors: Seung Ho
authors: SH
authors: Han
authors: Jaeyong
authors: J
authors: Yee
authors: Chan
authors: C
authors: Kim
authors: Sun Seek
authors: SS
authors: Min
keywords: Hippocampus; Long-term potentiation (LTP); Phorbol 12-myristate 13-acetate; Protein kinase C (PKC); Synaptic plasticity