School of Pharmacy, Hyogo Medical University, Kobe, Hyogo, 650-8530, Japan.
Laboratory of Basic Pain Research, Hyogo Medical University, Kobe, Hyogo, 650-8530, Japan.
Mol Brain. 2023 Jan 17;16(1):8. doi: 10.1186/s13041-023-01000-6.
Saltatory conduction is the propagation of action potentials along myelinated nerves, which enables fast propagation through the node of Ranvier. Recently, we demonstrated that K2P channels, TWIK-related K channel-1 (TREK-1), and TWIK-related arachidonic acid-activated K + channel (TRAAK), are highly expressed in the mammalian node of Ranvier of sensory nerves and have an important role in action potential repolarization instead of voltage-gated K channels. TREK-1/TRAAK channels are activated by membrane depolarization as well as various stimuli, such as temperature, pH, arachidonic acid, and mechanical membrane stretch. Although membrane mechanical stretch has been suggested to modulate action potential conduction, how membrane stretching modulates intrinsic electrophysiological properties at the node of Ranvier remains unclear. In the present study, we examined the effects of membrane stretch on neuronal membranes at the node of Ranvier in rat sciatic nerves. The single-channel conductance was approximately 90 pS at 80 mV. Membrane stretch increased the single-channel event numbers and open probability in a pressure-dependent manner. Consistent with single-channel activity, intra-pipette positive pressure increased outward leak currents and decreased membrane excitability in a whole-cell configuration. Furthermore, blockage of TREK-1/TRAAK channels by Ba reversed the changes in the intrinsic electrophysiological properties induced by intra-pipette pressure. These results indicate that the activation of mechanosensitive TREK-1/TRAAK channels may suppress neuronal excitability following axonal stretch. Our findings suggest that TREK-1/TRAAK channels may play an important role in the prevention of ectopic action potential discharge at the axon by intense mechanical nerve stretch under physiological conditions.
跳跃传导是动作电位沿有髓神经传播的方式，这使得它能够在郎飞结处快速传播。最近，我们证明 K2P 通道、TWIK 相关钾通道-1（TREK-1）和 TWIK 相关花生四烯酸激活的钾通道（TRAAK）在感觉神经的哺乳动物郎飞结中高度表达，并且在动作电位复极化中起重要作用，而不是电压门控钾通道。TREK-1/TRAAK 通道可被膜去极化以及各种刺激激活，如温度、pH 值、花生四烯酸和机械膜拉伸。尽管已经提出膜机械拉伸可以调节动作电位传导，但膜拉伸如何调节郎飞结处的固有电生理特性尚不清楚。在本研究中，我们检查了膜拉伸对大鼠坐骨神经郎飞结处神经元膜的影响。在 80 mV 时，单通道电导约为 90 pS。膜拉伸以压力依赖性的方式增加单通道事件数量和开放概率。与单通道活性一致，内管正压增加了外向漏电流，并降低了全细胞构型中的膜兴奋性。此外，内管正压引起的固有电生理特性的变化可被 Ba 阻断 TREK-1/TRAAK 通道所逆转。这些结果表明，机械敏感的 TREK-1/TRAAK 通道的激活可能抑制轴突拉伸后的神经元兴奋性。我们的发现表明，在生理条件下，强烈的机械神经拉伸可能会导致 TREK-1/TRAAK 通道激活，从而防止异位动作电位放电。
