Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294.
Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294
J Neurosci. 2022 Jun 22;42(25):4980-4994. doi: 10.1523/JNEUROSCI.0514-22.2022. Epub 2022 May 23.
Ion channels at the nodes of Ranvier (NRs) are believed to play essential roles in intrinsic electrophysiological properties and saltatory conduction of action potentials (AP) at the NRs of myelinated nerves. While we have recently shown that two-pore domain potassium (K2P) channels play a key role at the NRs of Aβ-afferent nerves, K channels and their functions at the NRs of mammalian motor nerves remain elusive. Here we addressed this issue by using preparations of lumbar spinal ventral nerves from both male and female rats and the pressure-patch-clamp recordings at their NRs. We found that depolarizing voltages evoked large noninactivating outward currents at NRs. The outward currents could be partially inhibited by voltage-gated K channel blockers, largely inhibited by K2P blockers and cooling temperatures. Inhibition of the outward currents by voltage-gated K channel blockers, K2P blockers, or cooling temperatures significantly altered electrophysiological properties measured at the NRs, including resting membrane potential, input resistance, AP width, AP amplitude, AP threshold, and AP rheobase. Furthermore, K2P blockers and cooling temperatures significantly reduced saltatory conduction velocity and success rates of APs in response to high-frequency stimulation. Voltage-gated K channel blockers reduced AP success rates at high-frequency stimulation without significantly affecting saltatory conduction velocity. Collectively, both K2P and voltage-gated K channels play significant roles in intrinsic electrophysiological properties and saltatory conduction at NRs of motor nerve fibers of rats. The effects of cooling temperatures on saltatory conduction are at least partially mediated by K2P channels at the NRs. Ion channels localized at the NRs are believed to be key determinants of saltatory conduction on myelinated nerves. However, ion channels and their functions at the NRs have not been fully studied in different types of mammalian myelinated nerves. Here we use the pressure-patch-clamp recordings to show that both K2P and voltage-gated K channels play significant roles in intrinsic electrophysiological properties and saltatory conduction at NRs of lumbar spinal ventral nerves of rats. Furthermore, cooling temperatures exert effects on saltatory conduction via inhibition of ion channels at the NRs. Our results provide new insights into saltatory conduction on myelinated nerves and may have physiological as well as pathologic implications.
郎飞结处的离子通道被认为在有髓神经郎飞结处动作电位（AP）的固有电生理特性和跳跃传导中发挥重要作用。虽然我们最近已经表明，双孔域钾（K2P）通道在 Aβ传入神经的郎飞结处发挥关键作用，但哺乳动物运动神经郎飞结处的 K 通道及其功能仍然难以捉摸。在这里，我们通过使用雄性和雌性大鼠的腰椎脊髓腹神经的准备以及在其郎飞结处的压力贴附式记录来解决这个问题。我们发现，去极化电压在郎飞结处诱发大的非失活外向电流。外向电流可被电压门控 K 通道阻断剂部分抑制，被 K2P 阻断剂和冷却温度强烈抑制。电压门控 K 通道阻断剂、K2P 阻断剂或冷却温度对郎飞结处测量的电生理特性的抑制，包括静息膜电位、输入电阻、AP 宽度、AP 幅度、AP 阈值和 AP 强度，显著改变了电生理特性。此外，K2P 阻断剂和冷却温度显著降低了高频刺激时 AP 的跳跃传导速度和成功率。电压门控 K 通道阻断剂降低了高频刺激时的 AP 成功率，而对跳跃传导速度没有显著影响。总的来说，K2P 和电压门控 K 通道在大鼠运动神经纤维的郎飞结处的固有电生理特性和跳跃传导中都发挥重要作用。冷却温度对跳跃传导的影响至少部分是通过郎飞结处的 K2P 通道介导的。位于郎飞结处的离子通道被认为是有髓神经跳跃传导的关键决定因素。然而，不同类型的哺乳动物有髓神经郎飞结处的离子通道及其功能尚未得到充分研究。在这里，我们使用压力贴附式记录来显示，K2P 和电压门控 K 通道在大鼠腰椎脊髓腹神经的郎飞结处的固有电生理特性和跳跃传导中都发挥重要作用。此外，冷却温度通过抑制郎飞结处的离子通道对跳跃传导产生影响。我们的结果为有髓神经的跳跃传导提供了新的见解，并可能具有生理和病理意义。
