Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260.
Departments of Chemistry.
J Neurosci. 2020 Apr 29;40(18):3504-3516. doi: 10.1523/JNEUROSCI.2415-19.2020. Epub 2020 Apr 7.
The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated along the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions: A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relatively consistent AP duration, and an end region near the tip of nerve terminal branches where the AP is briefer. We hypothesize that these measured changes in the AP waveform along the length of the motor nerve terminal may explain the proximal-distal gradient in transmitter release previously reported at the frog NMJ. The AP waveform plays an essential role in determining the behavior of neurotransmission at the presynaptic terminal. Although the frog NMJ is a model synapse for the study of synaptic transmission, there are many unknowns centered around the shape and propagation of its presynaptic AP waveform. Here, we demonstrate that the presynaptic terminal of the frog NMJ has a very brief AP waveform and that the motor nerve terminal contains three distinct electrical regions. We propose that the changes in the AP waveform as it propagates along the terminal can explain the proximal-distal gradient in transmitter release seen in electrophysiological studies.
动作电位（AP）波形控制电压门控钙通道的开启，并为钙离子流的驱动力做出贡献，从而触发突触前神经末梢的神经递质释放。尽管青蛙的神经肌肉接头（NMJ）长期以来一直是神经递质释放研究的模型突触，但它的突触前 AP 波形从未被直接研究过，因此 AP 波形的形状及其在这个长突触前神经末梢中的传播方式尚不清楚。我们使用快速电压敏感染料，对雄性和雌性青蛙 NMJ 的突触前末梢的 AP 波形进行了成像，结果表明 AP 持续时间非常短暂，并沿末梢的整个长度主动传播。此外，根据在神经末梢长度的不同区域测量的 AP 波形，我们表明该末梢分为三个不同的电区：Ranvier 最后一个神经节之后的起始区，AP 最宽；中间区具有相对一致的 AP 持续时间；以及靠近神经末梢分支末端的结束区，AP 更短。我们假设，沿运动神经末梢长度测量的 AP 波形的这些变化可以解释先前在青蛙 NMJ 上报道的递质释放的近端-远端梯度。AP 波形在决定突触前末梢神经递质释放的行为中起着至关重要的作用。尽管青蛙 NMJ 是研究突触传递的模型突触，但围绕其突触前 AP 波形的形状和传播存在许多未知因素。在这里，我们证明了青蛙 NMJ 的突触前末梢具有非常短暂的 AP 波形，并且运动神经末梢包含三个不同的电区。我们提出，AP 波形在沿末梢传播时的变化可以解释在电生理研究中观察到的递质释放的近端-远端梯度。
