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Neuroscience 1952

A Quantitative Description of Membrane Current

Alan Hodgkin & Andrew Huxley

The nerve impulse, turned into equations: voltage-gated ions that fire an all-or-nothing spike.

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In depth · the introduction

Every thought, heartbeat and twitch is a tiny electrical pulse — and in 1952 two scientists wrote down the exact equations that make it fire.

The big idea

A nerve cell rests with its inside about 65 thousandths of a volt more negative than its outside, like a charged battery, held that way by unequal amounts of sodium and potassium ions on the two sides. A nerve impulse is a sudden, travelling reversal of that voltage. Hodgkin and Huxley showed it happens because the membrane carries tiny voltage-controlled gates: when the voltage climbs past a threshold, sodium gates fly open and sodium floods in, shooting the voltage upward; a moment later they snap shut and potassium gates open, letting potassium out and resetting it.

Their achievement was to measure exactly how those gates open and close, and to capture it in a handful of equations precise enough to predict the whole pulse — its height, its speed, even the brief 'dead time' before the nerve can fire again.

How it came about

The work hinged on an unlikely hero: the giant axon of the squid, a nerve fibre so thick — up to a millimetre — that wires could be threaded inside it. Working in Cambridge and at the Plymouth marine laboratory, Alan Hodgkin and Andrew Huxley, with Bernard Katz, invented the 'voltage clamp,' a feedback circuit that holds the membrane at a chosen voltage and reads off the current. The Second World War interrupted everything for years.

When they returned, they measured the sodium and potassium currents in painstaking detail, then — with no electronic computer available — spent weeks turning the handle of a mechanical desk calculator to solve their equations. The nerve impulse they computed matched the real one, down to its shape and speed. They shared the 1963 Nobel Prize.

Why it mattered

For the first time, a living signal had been reduced to mathematics you could solve and trust. It showed that biology obeys physics down to the millivolt, and it created the template for modelling any electrically active cell — neurons, heart muscle, hormone-secreting cells. Modern brain simulations, cardiac drug testing and neural prosthetics all descend from these equations.

A way to picture it

Picture a line of dominoes that can stand themselves back up. Nudge the first one — the stimulus — only gently and nothing happens; it wobbles and steadies. Tip it past a certain angle and it falls, knocking the next, which knocks the next: an unstoppable wave that is the same size no matter how hard you pushed. That is 'all-or-nothing.' The sodium gates are the falling; the potassium gates are the mechanism that stands each domino back up, ready — after a short pause — to fire again.

Interactive Hodgkin–Huxley simulator: a slider sets how strong a brief shock is; the membrane voltage is plotted over a few milliseconds. A weak shock makes the line dip and recover; once the stimulus passes threshold, the line leaps into a full spike of about +40 mV that is the same height however much harder you push.

Where it sits

In the 1780s Galvani found that electricity moves muscle; around 1902 Bernstein guessed the impulse was an ion effect. Hodgkin and Huxley turned the guess into exact, testable equations — the same leap from description to mechanism that Watson and Crick made for heredity a year later. From here the line runs to today's atomic channel structures, to optogenetics, and to the conductance-based models behind large-scale brain simulation.

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.
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Physiological Laboratory, Cambridge · received 10 March 1952