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 membranbe of sk- etal
muscles thereby decreasing background membrane noise. In order to reduce the dominant source
of background noise-the leakage shunt under the pipet rim between m- the muscle membrane had to
be treated brane and gla- enzymatically. Despite these early limitations a new te- nique was
born -the patch-clamp technique. The final bre- through came in 1981 when the same authors in
collaboration with 0. P. Hamill A. Marty and F. J. Sigworth developed the gigaohm seal. Not
only did this improve the quality of recordings it was now possible to gently pull the
membrane patch with the attached pipet off the cell and study its trapped ion channels in
isolation. 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 technique is really a
sophisticated voltage-clamp technique and also allows for the altering of cytoplasmic
constituents if the experimenter so wishes. The first part of Patch-Clamp Applications and
Protocols presents modern developments associated with the techn- ogy of patch-clamp electrodes
of cell-free ion channel reco- ing and of the whole-cell patch-clamp technique.
