TY - JOUR
T1 - β-Phorbol ester-induced enhancement of exocytosis in large mossy fiber boutons of mouse hippocampus
AU - Hikima, Takuya
AU - Araki, Rikita
AU - Ishizuka, Toru
AU - Yawo, Hiromu
N1 - Funding Information:
Acknowledgments We thank S. Sakai for experimental assistance and discussion, Y. Sugiyama and H. Wang for comments on the manuscript, and B. Bell for reading the manuscript. This work was sponsored by Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST) and partly supported by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, Global COE Program (Basic & Translational Research Centre for Global Brain Science), MEXT, Strategic Research Program for Brain Sciences (SRPBS), MEXT, The Naito Foundation and The Novartis Foundation (Japan) for the Promotion of Science.
PY - 2009/7
Y1 - 2009/7
N2 - β-Phorbol esters (BPE), synthetic analogues of diacylglycerol (DAG), induce the potentiation of transmission in many kinds of synapses through activating the C1 domain-containing receptors. However, their effects on synaptic vesicle exocytosis have not yet been investigated. Here, we evaluated the vesicular exocytosis directly from individual large mossy fiber boutons (LMFBs) in hippocampal slices from transgenic mice that selectively express synaptopHluorin (SpH). We found that the activity-dependent increment of SpH fluorescence (ΔSpH) was enhanced by 4β-phorbol 12,13-diacetate (PDAc), one of the BPEs, without influencing the recycled component of SpH. These PDAc effects on ΔSpH were almost completely inhibited by staurosporine, a non-selective antagonist of protein kinases. However, intermittent synaptic transmission was still potentiated through a staurosporine-resistant mechanism. The staurosporine-sensitive cascade may facilitate the vesicle replenishment, thus maintaining the fidelity of transmission at a high level during repetitive firing of the presynaptic neuron.
AB - β-Phorbol esters (BPE), synthetic analogues of diacylglycerol (DAG), induce the potentiation of transmission in many kinds of synapses through activating the C1 domain-containing receptors. However, their effects on synaptic vesicle exocytosis have not yet been investigated. Here, we evaluated the vesicular exocytosis directly from individual large mossy fiber boutons (LMFBs) in hippocampal slices from transgenic mice that selectively express synaptopHluorin (SpH). We found that the activity-dependent increment of SpH fluorescence (ΔSpH) was enhanced by 4β-phorbol 12,13-diacetate (PDAc), one of the BPEs, without influencing the recycled component of SpH. These PDAc effects on ΔSpH were almost completely inhibited by staurosporine, a non-selective antagonist of protein kinases. However, intermittent synaptic transmission was still potentiated through a staurosporine-resistant mechanism. The staurosporine-sensitive cascade may facilitate the vesicle replenishment, thus maintaining the fidelity of transmission at a high level during repetitive firing of the presynaptic neuron.
KW - Exocytosis
KW - Munc13-1
KW - PKC
KW - Presynaptic mechanism
KW - Synaptic plasticity
KW - Synaptic transmission
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U2 - 10.1007/s12576-009-0031-0
DO - 10.1007/s12576-009-0031-0
M3 - Article
C2 - 19340534
AN - SCOPUS:67650677791
VL - 59
SP - 263
EP - 274
JO - The Journal of Physiological Sciences
JF - The Journal of Physiological Sciences
SN - 1880-6546
IS - 4
ER -