Re-evaluation of phorbol ester-induced potentiation of transmitter release from mossy fibre terminals of the mouse hippocampus

Izumi Honda, Haruyuki Kamiya, Hiromu Yawo

    Research output: Contribution to journalArticle

    37 Citations (Scopus)

    Abstract

    1. To investigate the mechanisms by which phorbol esters potentiate transmitter release from mossy fibre terminals we used fura dextran to measure the intraterminal Ca2+ concentration in mouse hippocampal slices. 2. A phorbol ester, phorbol 12,13-diacetate (PDAc), potentiated the field excitatory post-synaptic potential (fEPSP) slope. PDAc also enhanced the stimulation-dependent increase of [Ca2+]i in the mossy fibre terminal (Δ[Ca2+]pre). The magnitude of the PDAc-induced fEPSP potentiation (463 ± 57% at 10 μM) was larger than that expected from the enhancement of Δ[Ca2+]pre (153 ± 5%). 3. The Δ[Ca2+]pre was suppressed by ω-agatoxin IVA (ω- AgTxIVA, 200 nM), a P/Q-type Ca2+ channel-specific blocker, by 31%. The effect of PDAc did not select between ω-AgTxIVA-sensitive and - resistant components. 4. The PDAc-induced potentiation of the fEPSP slope was partially antagonized by the protein kinase C (PKC) inhibitor bisindolymaleimide I (BIS-I, 10 μM), whereas the Δ[Ca2+]pre was completely blocked by BIS-I. Although the BIS-I-sensitive fEPSP potentiation was accompanied by a reduction of the paired-pulse ratio (PPR), the BIS-I-resistant component was not. 5. Whole-cell patch clamp recording from a CA3 pyramidal neuron in a BIS-I-treated slice demonstrated that PDAc (10 μM) increased the frequency of miniature excitatory postsynaptic currents (mEPSCs, 259 ± 33% of control) without a noticeable change in their amplitude (102 ± 5% of control). 6. These results suggest that PKC potentiates transmitter release by at least two distinct mechanisms, one Δ[Ca2+]pre dependent and the other Δ[Ca2+]pre independent. In addition, some phorbol ester-mediated potentiation of synaptic transmission appears to occur without activating PKC.

    Original languageEnglish
    Pages (from-to)763-776
    Number of pages14
    JournalJournal of Physiology
    Volume529
    Issue number3
    DOIs
    Publication statusPublished - 2000 Dec 15

    ASJC Scopus subject areas

    • Physiology

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