My overview starts in the middle of the 19th century with three important observations. In its whole-cell configuration it was the solution to measure voltage clamp currents in small cells. The patch technique has been proven to be exceptionally versatile. The patch electrode made it possible to descend to the molecular level and record single ionic channel activity. An improvement of this electrode was the next major (r)evolution. At the same time transmembrane measurements were made possible in smaller cells by the introduction of the microelectrode. Application of the newly developed voltage clamp method for measuring ionic currents, resulted in the formulation of the ionic theory. This was the case with the use of the squid giant axon, allowing the insertion of “large” intracellular electrodes and derivation of transmembrane potentials. Technical innovations make discoveries possible. The period covered starts with Bernstein's formulation of the membrane hypothesis and the measurement of the nerve and muscle action potential. The aim of this review was to provide an overview of the most important stages in the development of cellular electrophysiology.
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