PDF(Pubmed)
Abstract：
The back-propagation of an action potential (AP) from the axon/soma to the dendrites plays a central role in dendritic integration. This process involves an intricate orchestration of various ion channels, but a comprehensive understanding of the contribution of each channel type remains elusive. In this study, we leverage ultrafast membrane potential recordings (Vm) and Ca2+ imaging techniques to shed light on the involvement of N-type voltage-gated Ca2+ channels (VGCCs) in layer-5 neocortical pyramidal neurons\' apical dendrites. We found a selective interaction between N-type VGCCs and large-conductance Ca2+-activated K+ channels (BK CAKCs). Remarkably, we observe that BK CAKCs are activated within a mere 500 μs after the AP peak, preceding the peak of the Ca2+ current triggered by the AP. Consequently, when N-type VGCCs are inhibited, the early broadening of the AP shape amplifies the activity of other VGCCs, leading to an augmented total Ca2+ influx. A NEURON model, constructed to replicate and support these experimental results, reveals the critical coupling between N-type and BK channels. This study not only redefines the conventional role of N-type VGCCs as primarily involved in presynaptic neurotransmitter release but also establishes their distinct and essential function as activators of BK CAKCs in neuronal dendrites. Furthermore, our results provide original functional validation of a physical interaction between Ca2+ and K+ channels, elucidated through ultrafast kinetic reconstruction. This insight enhances our understanding of the intricate mechanisms governing neuronal signaling and may have far-reaching implications in the field.
摘要：
从轴突/体细胞到树突的动作电位（AP）的反向传播在树突整合中起着核心作用。这个过程涉及各种离子通道的复杂编排，但是对每个频道类型的贡献的全面了解仍然难以捉摸。在这项研究中,我们利用超快膜电位记录（Vm）和Ca2成像技术来揭示N型电压门控Ca2通道（VGCC）在5层新皮质锥体神经元\'顶端树突中的参与。我们发现N型VGCC与大电导Ca2激活的K通道（BKCAKCs）之间存在选择性相互作用。值得注意的是,我们观察到BKCAKCs在AP峰值后的仅500μs内被激活，在AP触发的Ca2+电流的峰值之前。因此,当N型VGCC被抑制时，AP形状的早期扩大放大了其他VGCC的活性，导致总Ca2+流入增加。一个神经元模型,为了复制和支持这些实验结果，揭示了N型和BK通道之间的临界耦合。这项研究不仅重新定义了N型VGCCs主要参与突触前神经递质释放的常规作用，而且还确立了它们作为神经元树突中BKCAKCs激活剂的独特而重要的功能。此外，我们的结果提供了Ca2+和K+通道之间物理相互作用的原始功能验证，通过超快动力学重建阐明。这种见解增强了我们对控制神经元信号传导的复杂机制的理解，并可能在该领域具有深远的意义。
