Presynaptic mechanism for phorbol ester-induced synaptic potentiation.
Phorbol ester facilitates transmitter release at a variety of synapses, and the phorbol ester-induced synaptic potentiation (PESP) is a model for presynaptic facilitation. To address the mechanism underlying PESP, we have made paired whole-cell recordings from the giant presynaptic terminal, the calyx of Held, and its postsynaptic target in the medial nucleus of the trapezoid body in rat brainstem slices. Phorbol ester potentiated EPSCs without affecting either presynaptic calcium currents or potassium currents. Protein kinase C inhibitors applied from outside or injected directly into the presynaptic terminal attenuated the PESP. Furthermore, presynaptic loading of a synthetic peptide with the sequence of the N-terminal domain of Doc2alpha interacting with Munc13-1 (Mid peptide) significantly attenuated PESP, whereas mutated Mid peptide had no effect. We conclude that the target of the presynaptic facilitatory effect of phorbol ester resides downstream of calcium influx and may involve both protein kinase C and Doc2alpha - Munc13-1 interaction.
Hori
T
T
Department of Neurophysiology, University of Tokyo Faculty of Medicine, Tokyo 113-0033 Japan.
Takai
Y
Y
Takahashi
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001933:Brain Stem / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009847:Olivary Nucleus / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D011789:Quantum Theory; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D002135:Calcium-Binding Proteins; C490419:Doc2a protein, rat; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D011994:Recombinant Proteins; C485548:UNC13B protein, human; C103912:Unc13a protein, rat; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D002118:Calcium