Patch-clamp electrophysiology

The voltage and ion currents of a single simulated neuron, and the effects of drugs that block its channels.

Guided experiment: Recording a neuron with patch clamp.

Patch clamp records the electrical activity of a single cell through a fine glass pipette sealed onto its membrane. In current clamp the experimenter injects current and records the membrane voltage; in voltage clamp the voltage is held at chosen values and the currents that flow through ion channels are recorded. Neher and Sakmann used the technique to record the current through single ion channels (Neher and Sakmann, 1976).

Design the experiment

Questions to investigate

Find the smallest current step that makes the neuron fire. This is the rheobase.
Run a series of current steps. How does the firing rate depend on the injected current?
Apply tetrodotoxin (TTX), which blocks voltage-gated sodium channels. What happens to the action potential?
Apply tetraethylammonium (TEA), which blocks potassium channels. Why does the action potential become longer?
In voltage clamp, run a series of steps and find the voltage at which the sodium current reverses direction.
Raise the temperature. How do the speed and shape of the action potential change?

In a real laboratory

Recordings are made from neurons in thin brain slices or in culture, viewed through a microscope. A micromanipulator positions the pipette, and an amplifier controls current or voltage. The seal between pipette and membrane must exceed one gigaohm. Studies record from many cells in several animals, report how cells were selected and excluded, and require approval by an Institutional Animal Ethics Committee (in India, under the CCSEA and the Prevention of Cruelty to Animals Act 1960; elsewhere, the equivalent national body).

How the simulation works

The neuron is the Hodgkin–Huxley model of the squid giant axon: a single compartment with voltage-gated sodium and potassium channels and a leak, at 6.3 °C, the temperature of the original experiments (Hodgkin and Huxley, 1952). Mammalian neurons are usually recorded at room temperature or at 32 to 35 °C and express many more types of channel, so their firing differs in detail. Currents are given in µA/cm². In a small cell of about 1000 µm² (10 pF), 1 µA/cm² is about 10 pA, the same number as in pA/pF, the unit laboratories report. Drug block scales the maximum conductance of the channel, and temperature speeds channel kinetics with a Q10 of 3. Voltage clamp is ideal, with no pipette resistance.

Hodgkin, A. L., & Huxley, A. F. (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. Journal of Physiology, 117(4), 500–544. https://doi.org/10.1113/jphysiol.1952.sp004764
Neher, E., & Sakmann, B. (1976). Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature, 260(5554), 799–802. https://doi.org/10.1038/260799a0

About the simulations

Each simulator is a simplified version of a published model of cells, signals, instruments or behaviour, and runs in the web browser. The simulations show how the techniques work and how design choices change the results; they do not replace training in a laboratory.

All data are simulated and generated afresh on each run, so results vary between runs, as in real experiments. Nothing is stored or sent: designs and results are lost when the page is closed, unless the protocol is copied or the data file is downloaded.

Last updated 20 October 2026