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Re‐evaluation of phorbol ester‐induced potentiation of transmitter release from mossy fibre terminals of the mouse hippocampus
Author(s) -
Honda Izumi,
Kamiya Haruyuki,
Yawo Hiromu
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00763.x
Subject(s) - excitatory postsynaptic potential , long term potentiation , chemistry , protein kinase c , postsynaptic potential , hippocampal formation , biophysics , endocrinology , biology , phosphorylation , biochemistry , receptor
1 To investigate the mechanisms by which phorbol esters potentiate transmitter release from mossy fibre terminals we used fura dextran to measure the intraterminal Ca 2+ concentration in mouse hippocampal slices. 2 A phorbol ester, phorbol 12,13‐diacetate (PDAc), potentiated the field excitatory postsynaptic potential (fEPSP) slope. PDAc also enhanced the stimulation‐dependent increase of [Ca 2+ ] i in the mossy fibre terminal (Δ[Ca 2+ ] pre ). The magnitude of the PDAc‐induced fEPSP potentiation (463 ± 57 % at 10 μM) was larger than that expected from the enhancement of Δ[Ca 2+ ] pre (153 ± 5 %). 3 The Δ[Ca 2+ ] pre was suppressed by ω‐agatoxin IVA (ω‐AgTx IVA , 200 nM), a P/Q‐type Ca 2+ channel‐specific blocker, by 31 %. The effect of PDAc did not select between ω‐AgTx IVA ‐sensitive and ‐resistant components. 4 The PDAc‐induced potentiation of the fEPSP slope was partially antagonized by the protein kinase C (PKC) inhibitor bisindolylmaleimide I (BIS‐I, 10 μM), whereas the Δ[Ca 2+ ] 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[Ca 2+ ] pre dependent and the other Δ[Ca 2+ ] pre independent. In addition, some phorbol ester‐mediated potentiation of synaptic transmission appears to occur without activating PKC.