Electrophysiology

Electrophysiology is the direct measurement of electrical signals in living cells and tissue. Where most pharmacological methods infer a drug's effect from binding affinity or downstream messenger changes, electrophysiology records the actual current flowing through an ion channel or the actual voltage across a cell membrane — in real time, as the compound is applied.

The technique can reveal nuance that binding assays cannot. A substance may occupy a receptor and still produce a complex effect — partially activating it, slowing its kinetics, blocking it in a voltage-dependent way — distinctions only an electrical recording makes visible. It sits at the most direct end of the spectrum between a drug molecule and what happens to a neuron.

How it works · its role

The foundational method is the patch clamp, developed in the late 1970s. A fine glass pipette is sealed against a cell membrane, isolating a small patch containing one or a few ion channels. The experimenter can then hold the voltage fixed (voltage clamp) and watch current flow as a drug arrives, or hold the current fixed (current clamp) and watch how the membrane potential changes.

Preparations vary by question. Single-channel recordings from isolated cells reveal the molecular behaviour of one channel type in isolation. Field recordings in a living brain slice capture the collective firing of thousands of neurons, showing how a compound shifts network activity rather than just one protein.

The readout is a current trace over time — a direct electrical signature of what the drug is doing, updated millisecond by millisecond.

Relevance to substances & effects

Many substance classes produce their characteristic effects primarily through ion channels, and electrophysiology is what established those mechanisms with precision. Benzodiazepines, barbiturates, and alcohol all enhance GABA-A currents — a finding confirmed by patch clamp recordings showing longer or more frequent channel opening. Ketamine and PCP block NMDA channels in a use-dependent way that only recordings can capture directly.

Serotonergic psychedelics act mainly at the 5-HT₂A receptor, a G-protein-coupled receptor that does not conduct ions itself, so electrophysiology contributes here by showing downstream shifts in membrane excitability and cortical oscillation patterns rather than direct channel effects.

For most compounds in this encyclopedia, no published electrophysiology data exists. The technique is time-intensive and requires specialist equipment; it is typically applied to major drug targets with substantial research funding behind them. Where electrophysiology data does exist for a substance, it is referenced in that entry's pharmacology section.