Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut.
Connecticut Institute for the Brain and Cognitive Sciences, University of Connecticut, Storrs, Connecticut.
Adv Physiol Educ. 2022 Dec 1;46(4):693-702. doi: 10.1152/advan.00171.2021. Epub 2022 Sep 29.
Since its discovery in the mid-20th century, the Hodgkin-Huxley biophysical model of the squid giant axon's (SGA's) neurophysiology has traditionally served as the basis for the teaching of action potential (AP) dynamics in the physiology classroom. This model teaches that leak conductances set membrane resting potential; that fast, inactivating, voltage-gated sodium channels effect the SGA AP upstroke; and that delayed, rectifying, noninactivating voltage-gated potassium channels carry AP repolarization and the early part of the afterhyperpolarization (AHP). This model serves well to introduce students to the fundamental ideas of resting potential establishment and maintenance, as well as basic principles of AP generation and propagation. Furthermore, the Hodgkin-Huxley SGA model represents an excellent and accessible starting point for discussion of the concept of AP threshold and the role of passive electrical properties of the neuron. Additionally, the introduction of the Hodgkin-Huxley model of the SGA AP permits the integration of physiological principles, as instructors ask students to apply previously studied principles of transporter and channel biophysics to the essential physiological phenomenon of electrical signal conduction. However, both some early observations as well as more recent evidence strongly suggest that this seminal invertebrate model of AP dynamics does not appropriately capture the full story for mammalian axons. We review recent evidence that mammalian axonal nodes of Ranvier repolarize largely (though not exclusively) through the activity of leak potassium-ion (K) conductances carried through two-pore domain (K) channels. We call for changes to physiology textbooks and curricula to highlight this remarkable difference in invertebrate and mammalian AP repolarization mechanisms. Historically, physiology courses have typically taught that action potential repolarization occurs exclusively due to the activation of delayed-rectifier voltage-gated potassium channels. Here, we review and highlight recent evidence that leak potassium channels of the two-pore domain (K) class may largely serve this repolarization role at mammalian nodes of Ranvier. We call for the inclusion of these ideas in physiology curricula at all levels, from high school to graduate school.
自 20 世纪中叶发现以来，鱿鱼巨大轴突（SGA）神经生理学的 Hodgkin-Huxley 生物物理学模型一直是生理学教室教授动作电位（AP）动力学的基础。该模型教导说，漏电导设定膜静息电位；快速、失活、电压门控钠通道影响 SGA AP 上升支；延迟、整流、非失活电压门控钾通道携带 AP 复极化和早期后超极化（AHP）。该模型很好地向学生介绍了建立和维持静息电位的基本概念，以及 AP 产生和传播的基本原理。此外，Hodgkin-Huxley SGA 模型代表了讨论 AP 阈值概念和神经元被动电学特性作用的一个极好且易于理解的起点。此外，引入 Hodgkin-Huxley SGA AP 模型允许将生理学原理整合在一起，因为教师要求学生将先前研究的转运蛋白和通道生物物理学原理应用于电信号传导这一基本生理现象。然而，一些早期观察结果和最近的证据强烈表明，这种开创性的无脊椎动物 AP 动力学模型并不完全适用于哺乳动物轴突。我们回顾了最近的证据，表明哺乳动物轴突郎飞结的复极化主要（尽管不是排他性）是通过通过双孔域（K）通道携带的漏钾离子（K）电导的活动来实现的。我们呼吁修改生理学教科书和课程，以突出无脊椎动物和哺乳动物 AP 复极化机制的这一显著差异。从历史上看，生理学课程通常教授动作电位复极化仅由于延迟整流电压门控钾通道的激活而发生。在这里，我们回顾并强调了最近的证据，即双孔域（K）类漏钾通道可能在很大程度上在哺乳动物郎飞结中发挥这种复极化作用。我们呼吁在从高中到研究生院的各级生理学课程中纳入这些想法。
