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

Izumi Honda, Haruyuki Kamiya, Hiromu Yawo

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    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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