Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Biophys J. 2022 Sep 20;121(18):3499-3507. doi: 10.1016/j.bpj.2022.08.006. Epub 2022 Aug 12.
It has been demonstrated experimentally that slow and fast conduction waves with distinct conduction velocities can occur in the same nerve system depending on the strength or the form of the stimulus, which give rise to two modes of nerve functions. However, the mechanisms remain to be elucidated. In this study, we use computer simulations of the cable equation with modified Hodgkin-Huxley kinetics and analytical solutions of a simplified model to show that stimulus-dependent slow and fast waves recapitulating the experimental observations can occur in the cable, which are the two stable conduction states of a bistable conduction behavior. The bistable conduction is caused by a positive feedback loop of the wavefront upstroke speed, mediated by the sodium channel inactivation properties. Although the occurrence of bistable conduction only requires the presence of the sodium current, adding a calcium current to the model further promotes bistable conduction by potentiating the slow wave. We also show that the bistable conduction is robust, occurring for sodium and calcium activation thresholds well within the experimentally determined ones of the known sodium and calcium channel families. Since bistable conduction can occur in the cable equation of Hodgkin-Huxley kinetics with a single inward current, i.e., the sodium current, it can be a generic mechanism applicable to stimulus-dependent fast and slow conduction not only in the nerve systems but also in other electrically excitable systems, such as cardiac muscles.
实验已经证明,根据刺激的强度或形式,同一神经系统中可能会出现具有不同传导速度的慢波和快波,从而产生两种神经功能模式。然而,其机制仍有待阐明。在本研究中,我们使用改良 Hodgkin-Huxley 动力学的电缆方程的计算机模拟和简化模型的解析解来表明,依赖于刺激的慢波和快波可以在电缆中重现实验观察到的情况,这是双稳态传导行为的两种稳定传导状态。双稳态传导是由波前上升速度的正反馈环引起的,这是由钠通道失活特性介导的。尽管双稳态传导的发生仅需要存在钠电流,但向模型中添加钙电流可以通过增强慢波来进一步促进双稳态传导。我们还表明,双稳态传导是稳健的,发生在钠和钙激活阈值内,这些阈值远低于已知的钠和钙通道家族的实验确定的阈值。由于双稳态传导可以发生在具有单一内向电流(即钠电流)的 Hodgkin-Huxley 动力学的电缆方程中,因此它可以是一种通用机制,适用于不仅在神经系统中,而且在其他可兴奋的电系统中,如心肌中的依赖于刺激的快波和慢波。