Calcium-Dependent Isoforms of Protein Kinase C Mediate Posttetanic Potentiation at the Calyx of Held

Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Neuron (Impact Factor: 15.05). 06/2011; 70(5):1005-19. DOI: 10.1016/j.neuron.2011.04.019
Source: PubMed


High-frequency stimulation leads to a transient increase in the amplitude of evoked synaptic transmission that is known as posttetanic potentiation (PTP). Here we examine the roles of the calcium-dependent protein kinase C isoforms PKCα and PKCβ in PTP at the calyx of Held synapse. In PKCα/β double knockouts, 80% of PTP is eliminated, whereas basal synaptic properties are unaffected. PKCα and PKCβ produce PTP by increasing the size of the readily releasable pool of vesicles evoked by high-frequency stimulation and by increasing the fraction of this pool released by the first stimulus. PKCα and PKCβ do not facilitate presynaptic calcium currents. The small PTP remaining in double knockouts is mediated partly by an increase in miniature excitatory postsynaptic current amplitude and partly by a mechanism involving myosin light chain kinase. These experiments establish that PKCα and PKCβ are crucial for PTP and suggest that long-lasting presynaptic calcium increases produced by tetanic stimulation may activate these isoforms to produce PTP.

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    • "Phorbol 12,13-dibutyrate (PDBu), a DAG analog, can enhance transmission by activating not only PKC Ca (Figure 1A) but also Ca 2+ -insensitive PKC isoforms and other presynaptic proteins (Brose and Rosenmund, 2002; Newton, 2010). At immature calyces, ∼35% of PDBu-mediated enhancement is independent of PKC Ca (Fioravante et al., 2011). We found that PDBu enhances release at functionally mature wild-type calyces (Figure 1C, black) but not at agematched αβ dko calyces (Figure 1C, purple). "
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    Full-text · Article · Aug 2014 · eLife Sciences
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    • "A previous study evaluated the effects of BIS-like PKC inhibitors on PTP as non-specific (Lee et al., 2008). However, the genetic evidence for an involvement of conventional PKCs (Fioravante et al., 2011) and for the PKC phosphorylation sites of Munc18-1 in PTP (present study), as well as our pharmacological evidence with specific peptide inhibitors, firmly establishes the role of PKC and Munc18-1 phosphorylation in PTP. An earlier study found that phorbol esters translocates PKCε at the calyx of Held (Saitoh et al., 2001). "
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    Full-text · Article · Feb 2014 · eLife Sciences
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    • "In addition, PKCα and PKCß are differentially effective in these two phenomena. PKCß makes a much larger contribution to PTP than PKCα (Fioravante et al., 2011), whereas PKCα and PKCß make comparable contributions to glycine-induced enhancement. The different calcium signals that induce these forms of plasticity may underlie the differential contributions of these isoforms. "
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