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Electrophysiology is a study of the electrical properties that exist within biological cells and tissues, and this has developed to include the ability of these cells to react to electrical current. To do this, researchers have had to measure the change of voltage and also the flow of electric current covering a variety of scales, ranging from places such as the heart to single-ion channel proteins.

The origin of electrophysiology goes back to the research of the German, Emil Heinrich Du Bois-Rey-mond, from Berlin who, during his work at the University of Berlin, decided to concentrate on electrical activity in nerve and muscle fibers. His initial work was on fish and that they were capable of generating electrical currents on their own. From this, he turned to researching electrical conduction along muscle and nerve fibers which led him into work on electrical stimulation of muscles. His work on nerve and muscle stimulation led to the two-volume work Untersuchungen über thierische Elektricität (Researches on Animal Electricity), the first volume being published in 1848, and the second volume was not published until 1884. The books are still regarded as pioneers in the field of scientific electrophysiology. Du Bois-Reymond collaborated with Hermann von Helmholtz, Carl Ludwig, and Erich von Brücke; and his work was continued and developed by French physician Jacques-Arsène D'Arsonval from the University of Poitiers, Limoges, and Paris. D'Arsonval started to use electricity to treat skin and mucous membranes with his work being known as D'Arsonvalization.

Traditionally, electrophysiology has involved the placing of electrodes on various biological tissues. These electrodes may range from needles and discs, and then to printed circuit boards, and even hollow tubes such as glass pipettes filled with electrolytes. The last of these, if small enough, have been used to pass electricity to a single cell, although sometimes it is has been found that it is not necessary for the electrode tip to physically touch the cell. The biological tissues can also vary considerably, ranging from living organisms, excised tissue, cells removed from excised tissue, artificially grown cells or tissue, or hybrids of these preparations.

The main drawback of these traditional (or classical) practices has been that these techniques have only allowed electrophysiologists to observe the effect of an electrical current at a single point within the volume of the tissue. This has led to the development of optical electrophysiology with practitioners eager to overcome that drawback. This, in turn, resulted in work on a variety of related fields such as electroantennography (covering the olfactory receptors in arthropods), electrocardiography (for treatment of the heart), electroclography (for treatment of eyes), electrocorticography (for treating the cerebral cortex), electroculography (for treatment of the muscles), electroencephalography (for treatment of the brain), and electroretinography (for treatment of the retina of eyes).

Electrophysiology relies on the accuracy of intracellar recording whereby scientists measure the voltage or current which crosses the membrane of the cell being treated. Research in this field resulted in Alan Lloyd Hodgkin, Andrew Fielding Huxley, and Australian Sir John Carew Eccles winning the Nobel Prize in Physiology or Medicine in 1963. Their research was largely conducted on the Atlantic squid, Loligo pealei, using the voltage clamp technique. Huxley was later knighted for his services to science, as was Alan Hodgkin. In 1967, Finnish-born Swedish physiologist, Ragnar Arthur Granit, and Americans George Wald and

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