The voltage clamp

The membrane is the experimenter’s enemy here: its conductances depend on voltage, and voltage depends on the currents through those conductances. Anything you do perturbs what you are trying to measure, and the action potential runs away from you.

The voltage clamp breaks the loop by closing a different one. An amplifier compares membrane potential against a command, and injects whatever current is needed to null the difference. Marmont and Kenneth Cole arrived at the method independently, at about the same time, and it is usually credited to both. Because voltage is now held, the conductances stop moving on their own — and the injected current becomes a direct read-out of the ionic current at that voltage.

Why it belongs on this site

It is a feedback amplifier used as a measuring instrument, and the reason it works is the ordinary reason feedback works: high loop gain makes the output track the command and makes the tracking insensitive to what the load is doing. Harold Black invented that idea in 1927 to make telephone repeaters behave. Two decades later it was pointed at an axon.

Everything in the Hodgkin–Huxley model rests on this. The conductance curves, the gating exponents, the whole quantitative account of excitability are voltage-clamp measurements. Without an instrument that could hold voltage constant, there was no way to separate the sodium and potassium currents, and the model could not have been written.

What it cost

Space clamp. The technique assumes the whole patch of membrane sits at one potential, which requires a preparation short enough or an electrode long enough that cable properties do not spoil it — hence the squid giant axon, and hence the axial-wire geometry. Extending the idea to small cells with real dendrites took another twenty-seven years and became the patch clamp.