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

J Physiol. 2000 Dec 15;529 Pt 3(Pt 3):763-76. doi: 10.1111/j.1469-7793.2000.00763.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • In Vitro Techniques
  • Indoles / pharmacology
  • Maleimides / pharmacology
  • Mice
  • Mossy Fibers, Hippocampal / drug effects*
  • Mossy Fibers, Hippocampal / metabolism*
  • Nerve Endings / drug effects*
  • Nerve Endings / metabolism*
  • Neurotransmitter Agents / metabolism*
  • Osmolar Concentration
  • Phorbol Esters / pharmacology*
  • Protein Kinase C / antagonists & inhibitors
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • omega-Agatoxin IVA / pharmacology
  • omega-Conotoxin GVIA / pharmacology


  • Calcium Channel Blockers
  • Indoles
  • Maleimides
  • Neurotransmitter Agents
  • Phorbol Esters
  • omega-Agatoxin IVA
  • phorbol-12,13-diacetate
  • omega-Conotoxin GVIA
  • Protein Kinase C
  • bisindolylmaleimide I
  • Calcium