title: Posttetanic potentiation critically depends on an enhanced Ca(2+) sensitivity of vesicle fusion mediated by presynaptic PKC.
abstract: Activity-dependent enhancement of transmitter release is a common form of presynaptic plasticity, but the underlying signaling mechanisms have remained largely unknown, perhaps because of the inaccessibility of most CNS nerve terminals. Here we investigated the signaling steps that underlie posttetanic potentiation (PTP), a form of presynaptic plasticity found at many CNS synapses. Direct whole-cell recordings from the large calyx of Held nerve terminals with the perforated patch-clamp technique showed that PTP was not mediated by changes in the presynaptic action potential waveform. Ca(2+) imaging revealed a slight increase of the presynaptic Ca(2+) transient during PTP ( approximately 15%), which, however, was too small to explain a large part of PTP. The presynaptic PKC pathway was critically involved in PTP because (i) PTP was occluded by activation of PKC with phorbol esters, and (ii) PTP was largely (by approximately two-thirds) blocked by the PKC inhibitors, Ro31-8220 or bisindolylmaleimide. Activation of PKC during PTP most likely acts directly on the presynaptic release machinery, because in presynaptic Ca(2+) uncaging experiments, activation of PKC by phorbol ester greatly increased the Ca(2+) sensitivity of vesicle fusion in a Ro31-8220-sensitive manner ( approximately 300% with small Ca(2+) uncaging stimuli), but only slightly increased presynaptic voltage-gated Ca(2+) currents ( approximately 15%). We conclude that a PKC-dependent increase in the Ca(2+) sensitivity of vesicle fusion is a key step in the enhancement of transmitter release during PTP.
authors: AG Synaptic Dynamics and Modulation, Department of Membrane Biophysics, Max-Planck-Institute for Biophysical Chemistry, D-37077 Göttingen, Germany.
authors: Natalya
authors: N
authors: Korogod
authors: Xuelin
authors: X
authors: Lou
authors: Ralf
authors: R
authors: Schneggenburger
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D002459:Cell Fusion; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D017774:Long-Term Potentiation / Q000502:physiology; D008301:Maleimides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D013746:Tetany / Q000503:physiopathology*
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D011493:Protein Kinase C; C088060:bisindolylmaleimide; D002118:Calcium; C064758:Ro 31-8220