Patch-Clamp Applications and Protocols

E. Neher and B. Sakman were the first to monitor the opening and closing of individual ion channels in membranes through conductivity measurements. In 1976, they used fire-polished micropipettes with a tip diameter of 3-5 micrometers to record currents from a small area of the skeletal muscle membrane, thereby reducing the background noise of the membrane. To minimize the dominant source of background noise—the leak current at the pipette edge between the muscle membrane and the glass—an enzymatic treatment of the membrane was necessary. Despite these early limitations, a new technique was born: the patch-clamp technique. The breakthrough came in 1981 when the same authors, in collaboration with O. P. Hamill, A. Marty, and F. J. Sigworth, developed the gigohm seal principle. This not only improved the quality of the recordings but also made it possible to gently pull the membrane patch away from the cell with the attached pipette.