patchclamp

Patch-clamp is a set of electrophysiological techniques used to measure ionic currents through channels in individual cells or patches of membrane. Developed in the 1970s by Erwin Neher and Bert Sakmann, it enables precise control of membrane potential and high-resolution recording of channel activity. A glass micropipette forms a gigaseal with a patch of membrane, allowing electrical access with minimal leak.

Four main configurations are used. In cell-attached mode, currents through channels in the patch are measured without rupturing the membrane. The inside-out and outside-out configurations involve excising the patch to expose the intracellular or extracellular surfaces, enabling study of modulators and ligands. In whole-cell mode, suction breaks the patch to give electrical access to the cell interior, allowing measurement of whole-cell currents. Patch-clamp is often performed in voltage-clamp mode, where the experimenter sets the membrane potential and records the resulting currents; current-clamp mode records membrane potential itself.

Applications span neuroscience and cardiology, pharmacology, and ion-channel research. It is used to characterize channel conductance and gating, assess drug effects, and investigate cellular pathologies. Advantages include high temporal resolution, the ability to isolate single-channel activity, and direct control of voltage. Limitations include technical difficulty, low throughput, sensitivity to seal quality and series resistance, and potential cellular perturbation during recording.

Recent trends include automation and high-throughput patch-clamp systems, as well as combinations with optical methods and fluorescence to correlate electrical signals with molecular events.