title: Re-evaluation of phorbol ester-induced potentiation of transmitter release from mossy fibre terminals of the mouse hippocampus.
abstract: 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. A phorbol ester, phorbol 12,13-diacetate (PDAc), potentiated the field excitatory postsynaptic potential (fEPSP) slope. PDAc also enhanced the stimulation-dependent increase of [Ca2+]i in the mossy fibre terminal (Delta[Ca2+]pre). The magnitude of the PDAc-induced fEPSP potentiation (463+/-57% at 10 microM) was larger than that expected from the enhancement of Delta[Ca2+]pre (153+/-5%). The Delta[Ca2+]pre was suppressed by omega-agatoxin IVA (omega-AgTxIVA, 200 nM), a P/Q-type Ca2+ channel-specific blocker, by 31%. The effect of PDAc did not select between omega-AgTxIVA-sensitive and -resistant components. The PDAc-induced potentiation of the fEPSP slope was partially antagonized by the protein kinase C (PKC) inhibitor bisindolylmaleimide I (BIS-I, 10 microM), whereas the Delta[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. Whole-cell patch clamp recording from a CA3 pyramidal neuron in a BIS-I-treated slice demonstrated that PDAc (10 microM) increased the frequency of miniature excitatory postsynaptic currents (mEPSCs, 259+/-33% of control) without a noticeable change in their amplitude (102+/-5% of control). These results suggest that PKC potentiates transmitter release by at least two distinct mechanisms, one Delta[Ca2+]pre dependent and the other Delta[Ca2+]pre independent. In addition, some phorbol ester-mediated potentiation of synaptic transmission appears to occur without activating PKC.
authors: Department of Neurophysiology, Tohoku University School of Medicine, Sendai 980-8575, Japan.
authors: I
authors: I
authors: Honda
authors: H
authors: H
authors: Kamiya
authors: H
authors: H
authors: Yawo
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects* / Q000378:metabolism*; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009994:Osmolar Concentration; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D007211:Indoles; D008301:Maleimides; D018377:Neurotransmitter Agents; D010703:Phorbol Esters; D020867:omega-Agatoxin IVA; C008874:phorbol-12,13-diacetate; D020866:omega-Conotoxin GVIA; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D002118:Calcium