Hori T, Takai Y, Takahashi T
Department of Neurophysiology, University of Tokyo Faculty of Medicine, Tokyo 113-0033 Japan.
J Neurosci. 1999 Sep 1;19(17):7262-7. doi: 10.1523/JNEUROSCI.19-17-07262.1999.
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.
佛波酯可促进多种突触处的递质释放，且佛波酯诱导的突触增强（PESP）是一种突触前易化模型。为了探究PESP的潜在机制，我们在大鼠脑干切片中对巨大突触前终末（Held壶腹）及其在梯形体内侧核中的突触后靶点进行了配对全细胞记录。佛波酯增强了兴奋性突触后电流（EPSCs），而不影响突触前钙电流或钾电流。从外部施加或直接注射到突触前终末的蛋白激酶C抑制剂减弱了PESP。此外，用与Munc13-1相互作用的Doc2α N端结构域序列的合成肽进行突触前加载（Mid肽）可显著减弱PESP，而突变的Mid肽则无此作用。我们得出结论，佛波酯突触前易化作用的靶点位于钙内流下游，可能涉及蛋白激酶C和Doc2α-Munc13-1相互作用。
