JOVANA
Library Glossary Getting Started Three Levels Fields How it works Mission
Join the mission
Back to the library
神经科学 1952

膜电流的定量描述

艾伦·霍奇金 与 安德鲁·赫胥黎

把神经冲动写成方程:电压门控的离子,发放一记「全或无」的尖峰。

Choose your version
In depth · the introduction

你的每一个念头、每一次心跳、每一下抽动,都是一记微小的电脉冲——而 1952 年,两位科学家写下了让它发放的精确方程。

核心想法

一个神经细胞静息时,内部比外部约负 65 毫伏,像一节充好电的电池,靠两侧钠、钾离子数量的不均等来维持。所谓神经冲动,就是这个电压一次突然的、行进着的反转。霍奇金与赫胥黎指出,这是因为膜上带着一些极小的、受电压控制的门:当电压升过一个阈值,钠门骤然打开、钠涌入,把电压猛地顶上去;一瞬之后它们又砰地关上,钾门打开,让钾流出、把电压复位。

他们的成就,是精确测出这些门如何开合,并把它凝成寥寥几个方程——精确到足以预言整个脉冲:它的高度、它的速度,乃至神经再次能够发放之前那段短暂的「死时间」。

它是如何诞生的

这项工作仰仗一位不太可能的主角:枪乌贼的巨轴突——一根粗到(可达一毫米)能往里穿电线的神经纤维。在剑桥与普利茅斯的海洋实验室,艾伦·霍奇金与安德鲁·赫胥黎,还有伯纳德·卡茨,发明了「电压钳」:一个反馈电路,把膜固定在选定的电压上,并读出电流。第二次世界大战曾让一切中断数年。

归来之后,他们极尽细致地测量了钠电流与钾电流,又因为没有电子计算机可用,花了几周时间用手摇一台机械台式计算器来求解方程。算出的神经冲动,连同它的形状与速度,都与真实的那一记吻合。他们分享了 1963 年的诺贝尔奖。

它为何重要

一个活生生的信号,第一次被化简为你能求解、又能信赖的数学。它表明生物学连到毫伏一级都服从物理,也为「为任何带电活动的细胞建模」立下了范本——神经元、心肌、分泌激素的细胞。今天的脑模拟、心脏药物测试与神经假体,全都承自这组方程。

一个可以想象的画面

想象一排能自己重新站起来的多米诺骨牌。只轻轻一碰第一张——那个刺激——什么也不会发生,它晃一晃又稳住了。可一旦把它推过某个角度,它就倒下,撞倒下一张、再下一张:一道挡不住的波,而且无论你推得多用力,它的大小始终如一。这就是「全或无」。钠门是那场倒下;钾门则是把每张骨牌重新扶正的机关——歇上一小会儿,便又能再次发放。

可交互的霍奇金–赫胥黎模拟器:滑块设定一记短促电击有多强;膜电压在几毫秒内被绘出。弱电击让线下沉后恢复;刺激一旦越过阈值,线便跃成一记约 +40 mV 的完整尖峰,无论你再加多大力,它的高度都一样。

它的位置

1780 年代,伽伐尼发现电能驱动肌肉;约 1902 年,伯恩斯坦猜想冲动是一种离子效应。霍奇金与赫胥黎把猜想变成了精确、可检验的方程——这与一年后沃森和克里克为遗传所做的、从「描述」到「机制」的跨越如出一辙。从这里,一条线通向今天原子级的通道结构、光遗传学,以及大规模脑模拟背后那些基于电导的模型。

The original document
Original source text
A. L. Hodgkin & A. F. Huxley · J. Physiol. 117 (1952): 500–544
This article concludes a series of papers concerned with the flow of electric current through the surface membrane of a giant nerve fibre (Hodgkin, Huxley & Katz, 1952; Hodgkin & Huxley, 1952 a–c). Its general object is to discuss the results of the preceding papers (Part I), to put them into mathematical form (Part II) and to show that they will account for conduction and excitation in quantitative terms (Part III).
Part I — The components of the membrane current
Current can be carried through the membrane either by charging the membrane capacity or by movement of ions through the resistances in parallel with the capacity. The ionic current is divided into components carried by sodium and potassium ions (I_Na and I_K), and a small 'leakage current' (I_l) made up by chloride and other ions.
Voltage-clamp records (from the preceding papers in the series) show that when the membrane is suddenly depolarised, the sodium conductance rises fast and then falls even though the depolarisation is maintained, while the potassium conductance rises later along an S-shaped curve and stays up. These two voltage- and time-dependent conductances, riding on a constant leak, are the whole of the ionic current.
Part II — Mathematical description of the membrane current
The total current is written as a capacitive term plus three ionic currents, each an Ohmic conductance times its driving force (V − E). The variable conductances are built from dimensionless gating variables m, h (sodium) and n (potassium), each between 0 and 1 and each obeying a first-order rate equation dx/dt = αₓ(V)(1−x) − βₓ(V)x. Fitting the clamp data gives g_Na = ḡ_Na·m³h and g_K = ḡ_K·n⁴, with the rate constants αₓ, βₓ expressed as functions of voltage.
Part III — Reconstruction of conduction and excitation
With no further assumptions, the equations are solved to reconstruct the action potential, the threshold, the refractory period, anode-break excitation, and — coupled to cable theory — the propagated impulse and its conduction velocity, all computed numerically by hand on a mechanical calculator and compared point-by-point with the measured records.
[ … ]
Physiological Laboratory, Cambridge · received 10 March 1952