Introduction to Patch-Clamp Technique

E. Neher and B. Sakman were the first to monitor the opening and closing of single ion channels and membranes by conductance measurements. In 1976, they used firepolished micropipets with a tip diameter of 3-5 pm to record currents from a small patch of the membrane of skeletal muscles, thereby decreasing background membrane noise.

In order to reduce the dominant source of background noise—the leakage shunt under the pipet rim between the muscle membrane and glass—enzymatic treatment of the membrane was necessary. Despite these early limitations, a new technique was born—the patch-clamp technique.

Development of the Gigaohm Seal

The breakthrough came in 1981 when the same authors, in collaboration with O. P. Hamill, A. Marty, and F. J. Sigworth, developed the gigaohm seal. This innovation improved the quality of recordings and made it possible to gently pull the membrane patch with the attached pipet off the cell to study its trapped ion channels in isolation.

Whole-Cell Patch-Clamp Technique

Another offshoot of the gigaohm seal technique was the whole-cell patch-clamp technique, in which the patch is ruptured without breaking the seal. This method is essentially a sophisticated voltage-clamp technique and allows for the alteration of cytoplasmic constituents if desired by the experimenter.

Modern Developments

The first part of Patch-Clamp Applications and Protocols presents modern developments related to the technology of patch-clamp electrodes, cell-free ion channel recording, and the whole-cell patch-clamp technique.