Furukawa Kei, Kawaguchi Shin-Ya
Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto, Japan.
Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Front Cell Neurosci. 2025 Jul 22;19:1633202. doi: 10.3389/fncel.2025.1633202. eCollection 2025.
In contrast to conventional view about the faithful signaling in neuronal axons by all-or-none action potentials, recent studies have shown that axons exhibit dynamic change in action potential waveforms and/or conduction velocities in a manner dependent on neuronal activity and/or inputs to axonal compartments from other neurons. It was recently shown that a well-known second messenger cAMP negatively regulates the axonal voltage-gated Na channels, which decreases the amplitude and conduction velocity of action potentials in axons of cerebellar Purkinje cells. To understand the signaling mechanism and physiological context of the cAMP-mediated action potential modulation, we studied the involvement of one of neuromodulators, adrenergic system, using direct patch-clamp recordings from axons and/or terminals of Purkinje cells. We demonstrate that Purkinje cell axons exhibit negative control of action potentials in amplitude and conduction velocity by β-adrenergic receptors in a manner dependent on the axonal length through specific reduction of axonal Na currents. On the other hand, β-adrenergic receptors increased presynaptic release probability without changing the amount of readily releasable vesicles in axon terminals of Purkinje cells. Together, our data highlight a physiological pathway to activate cAMP signaling to cause the axonal length-dependent dynamic changes in the timing and strength of synaptic transmission.
与传统观点认为神经元轴突通过全或无动作电位进行可靠信号传导不同，最近的研究表明，轴突在动作电位波形和/或传导速度方面呈现动态变化，其方式取决于神经元活动和/或来自其他神经元对轴突节段的输入。最近有研究表明，一种著名的第二信使环磷酸腺苷（cAMP）对轴突电压门控钠通道具有负调节作用，这会降低小脑浦肯野细胞轴突中动作电位的幅度和传导速度。为了理解cAMP介导的动作电位调制的信号传导机制和生理背景，我们利用对浦肯野细胞轴突和/或终末的直接膜片钳记录，研究了一种神经调质——肾上腺素能系统的参与情况。我们证明，浦肯野细胞轴突通过β - 肾上腺素能受体对动作电位的幅度和传导速度呈现负调控，其方式依赖于轴突长度，通过特异性降低轴突钠电流实现。另一方面，β - 肾上腺素能受体增加了浦肯野细胞轴突终末的突触前释放概率，而不改变易释放囊泡的数量。总之，我们的数据突出了一条激活cAMP信号传导的生理途径，以引起突触传递时间和强度上依赖于轴突长度的动态变化。
