Background
The advent of observation with the cognitive mind inevitably brought about theories to explain the events that had unfolded before an observer's eyes. Some of the more interesting theories are those concerned with the functioning of an animal system, like the human body. These ideas helped elucidate the invisible reason behind the physical function that was the basis for the initial scrutiny of the animal. Some of the more elaborate theories also proved to be hypotheses of the human system. Many times, due to taboos or other restrictions of the time, direct inspection of the human form was not allowed. Instead inferences were made based on dissections of other animal systems. These dissections answered some of the anatomical questions, both correctly and incorrectly. However, the motives driving physiological processes still remained a mystery. This deficiency in the theories of the human system lead to the invention of humors and fluids for the impetus of biological functioning. With the experiments of Luigi Galvani in electrophysiology, these ethereal body humors would forever be removed from the theories of the human body (Piccolino, 1998). Scientists after Galvani had a tangible justification for their observations of physiological processes.
Origins of Electrophysiology
Italian
Born in 1737 in Bologna, Luigi Galvani is often credited with the establishment of electrophysiology of nerve tissue. Galvani published the results of his eleven years of experimentation in 1791 in De Viribus Electricitatis in Motu Musculari Commentarius (Piccolino, 1998). In Galvani's work, frog legs with exposed crural nerves were subjected to electrical stimuli. Often the source of the electricity was a Leyden jar; however, other sources of electricity were also employed including electrical machines, Franklin magic squares, electrophorous, and the atmosphere. The atmospheric experiments closely resembled Benjamin Franklin's experiments with atmospheric electricity except Franklin played the role of the frog. The results of these experiments were far reaching within Galvani's time and into the future. People of all educational backgrounds wanted to reproduce and see for themselves the muscle contractions elicited by the application of electricity. A nephew of Galvani, Giovanni Aldini proposed the use of electricity to revitalize the dead. This idea supposedly inspired Mary Shelley's Frankenstein. Galvani's results were later replicated by Aldini in 1794, Von Humboldt in 1797, and Volta in 1800 (Goldensohn, 1998). However, Volta attributed Galvani's results to a current generated by the contact of two different metals. Due to the controversy over Galvani's conclusions and Volta's prestige, research on animal electricity, as Galvani called it, slowed to a standstill. The next advances occurred in 1838 with the publication of Carlo Matteucci's research. Matteucci created what was referred to as a biological pile, similar to a voltaic pile. Matteucci placed sectioned frog thighs in series, the intact portion directly in contact with the cut surface of the next thigh. The results showed that increasing the number of sections increased the measured current. This increase in current was due to the biologic muscle tissue and not the contact of the metal electrodes (Piccolino, 1998).
German
From Italy this research spread to Germany in the research of Emile du Bois-Reymond and Hermann von Helmholtz. The work of du Bois-Reymond was published in a two-volume book in 1848 and 1849 titled Untersuchungen uber Thierische Elektricitat or Investigations on Animal Electricity (Goldensohn, 1998). Most of du Bois-Reymond's work concerned nerve excitation, and he is credited with measuring what he called "negative Schwankung" or negative variation. This measurand was later termed action current or action potential (Piccolino, 1998). In 1850, a contemporary of du Bois-Reymond discovered a way to measure the speed of propagation of a nerve signal. Hermann von Helmholtz devised an innovative apparatus for his experiment. Time elapsed from the application of the electric stimulus until the physical contraction of the muscle was measured. The actual movement of the muscle opened the electric circuit and thereby terminated the application of the electric stimulus (Piccolino, 1998). This work was continued by two students of du Bois-Reymond, Julius Bernstein and Ludimar Hermann. Hermann proposed a theory that the signal could be propagated by a current flowing from an exciting section of the nerve to a section of the nerve that was initially at rest, Hermann local circuit theory. (Piccolino, 1998) Bernstein was the first to measure the time course of the action current. Bernstein also applied the idea of a selectively permeable membrane and the diffusion of ions to account for the difference in potential between the inside of cell and the outside (Piccolino, 1998; McAdams, 1995).
English
From the German schools the research in electrophysiology
moved to the English. One of the first theories developed was from H. P.
Bowditch in 1871. Bowditch observed that, once the electrical stimulus was
of sufficient strength to cause muscle contraction, increasing the stimulus
intensity did not strengthen the response from the muscle tissue (Piccolino,
1998). The major advances in electrophysiology in the twentieth century
began in 1934. This is when Alan Hodgkin began his research into the
physiology of nervous tissue. Hodgkin's first experiment resulted in
confirming Hermann's local circuit theory. Some time later, Cole and
Curtis and Hodgkin and Huxley all recorded the transmembrane potential of the
giant squid axon. Using this same type of axon in 1949, Hodgkin and Katz
explained that the action potential of the cell membrane was due to an increase
in membrane permeability to sodium ions. At rest the membrane was
permeable only to potassium ions; however, in an excited state, the influx of
sodium dominated the action potential (Piccolino, 1998). In 1949, the
invention of the voltage clamp by Cole and Marmont gave researchers a new tool
for the study of electrophysiology. This new tool was used in 1952 by
Hodgkin, Huxley, and Katz to further interpret the biological events behind the
action potential (Piccolino, 1998). However their research did not answer
all the questions concerning cellular electrophysiology. Researchers
where still unsure what controlled ion flow through the membrane, a pore-like
opening in the membrane or some transporter molecule. The idea of an ion
channel was introduced by Erwin Neher and Bert Sakmann in 1976 based on their
work with patch clamps. This discovery helped to further the scientific
knowledge of electrophysiology.