Department of Physiology, Showa University School of Medicine, Tokyo, 142-8555, Japan.
Pflugers Arch. 2023 Nov;475(11):1301-1314. doi: 10.1007/s00424-023-02857-1. Epub 2023 Sep 14.
Aconitine is a sodium channel opener, but its effects on the respiratory center are not well understood. We investigated the dose-dependent effects of aconitine on central respiratory activity in brainstem-spinal cord preparations isolated from newborn rats. Bath application of 0.5-5 μM aconitine caused an increase in respiratory rhythm and decrease in the inspiratory burst amplitude of the fourth cervical ventral root (C4). Separate application of aconitine revealed that medullary neurons were responsible for the respiratory rhythm increase, and neurons in both the medulla and spinal cord were involved in the decrease of C4 amplitude by aconitine. A local anesthetic, lidocaine (100 μM), or a voltage-dependent sodium channel blocker, tetrodotoxin (0.1 μM), partially antagonized the C4 amplitude decrease by aconitine. Tetrodotoxin treatment tentatively decreased the respiratory rhythm, but lidocaine tended to further increase the rhythm. Treatment with 100 μM riluzole or 100 μM flufenamic acid, which are known to inhibit respiratory pacemaker activity, did not reduce the respiratory rhythm enhanced by aconitine + lidocaine. The application of 1 μM aconitine depolarized the preinspiratory, expiratory, and inspiratory motor neurons. The facilitated burst rhythm of inspiratory neurons after aconitine disappeared in a low Ca/high Mg synaptic blockade solution. We showed the dose-dependent effects of aconitine on respiratory activity. The antagonists reversed the depressive effects of aconitine in different manners, possibly due to their actions on different sites of sodium channels. The burst-generating pacemaker properties of neurons may not be involved in the generation of the facilitated rhythm after aconitine treatment.
乌头碱是一种钠离子通道 opener，但它对呼吸中枢的作用尚不清楚。我们研究了乌头碱在新生大鼠离体脑干脊髓标本中对中枢呼吸活动的剂量依赖性影响。0.5-5 μM 乌头碱的浴应用引起呼吸节律增加和第四颈前根（C4）吸气爆发幅度减小。乌头碱的单独应用表明，延髓神经元负责呼吸节律增加，而延髓和脊髓中的神经元都参与了乌头碱引起的 C4 幅度减小。局部麻醉剂利多卡因（100 μM）或电压依赖性钠离子通道阻断剂河豚毒素（0.1 μM）部分拮抗了乌头碱引起的 C4 幅度减小。河豚毒素处理暂时降低了呼吸节律，但利多卡因倾向于进一步增加节律。用已知抑制呼吸起搏器活动的 100 μM 利鲁唑或 100 μM 氟芬那酸处理，不能减少乌头碱+利多卡因增强的呼吸节律。1 μM 乌头碱使预吸气、呼气和吸气运动神经元去极化。乌头碱后吸气神经元爆发节奏的易化消失在低钙/高镁突触阻断溶液中。我们显示了乌头碱对呼吸活动的剂量依赖性影响。拮抗剂以不同的方式逆转了乌头碱的抑制作用，可能是由于它们对钠离子通道不同部位的作用。神经元的爆发产生起搏器特性可能不参与乌头碱处理后易化节律的产生。
