The Generation of Bioelectric Potentials

EVER since Matteucci and DuBois Reymond established the fact that muscle and nerve activity is associated with bioelectric, potentials, it has been safe to assume that contraction of the heart must also have an electric correlate. Although Koelliker and Johannes Mueller actually were the first to succeed in demonstrating such electric activity, it was only when Einthoven, using a sufficiently sensitive string galvanometer, that the rapid development of the field began. Today the electrocardiogram is essential not only as a research tool but for the daily routine of cardiologists. However, bioelectric potentials are just signs of activity, they do not give any indications about the underlying mechanism. H. S. Gasser once compared them to the ticks of the clock. For an understanding and evaluation of these electric manifestations, be it of nerve and muscle or of the heart, knowledge of the mechanism is imperative. During the past decade considerable progress has been achieved in this respect. The following brief outline intends to give a picture of the mechanism of the generation of bioelectric potentials as it has emerged recently. The concentration of ions in the cell interior differs greatly from that in the outer environment. The concentration of sodium is low in contrast to that of the external fluid, the reverse is true for potassium ions. These ionic concentration gradients are, as has always been assumed, the source of EMF of bioelectric potentials. The "membrane theory", developed at the turn of the century, postulated that membranes are surrounded by a polarized membrane charged positively on the outside and negatively on the inside. In cells, capable of conducting impulses, such as nerve or muscle fibers, the ionic permeability of a stimulated active region increases, with the corresponding decline in electrical resistance. This leads to a depolarization or actually, as we know today, to a reverse of the charge. The difference of charge between active and resting points of the membrane leads to the generation of small currents which stimulate the adjacent region. There, the same process is repeated. In this way, successive parts of the membrane are activated and the impulses propagated along the axon. The availability of radioactive ions after World War II made it possible to measure precisely the ion movements.' We know today that there is a sudden influx of sodium ions into the cell interior, which explains the rising phase of the action potentials and a corresponding outflow of potassium during the falling phase. The permeability of the membrane for sodium ions increases by about 500 times. This raises the fundamental question: by what mechanism does the potential source of EMF, the ionic concentration gradients, inactive in rest, become suddenly effective? There must be a trigger action, a chemical process in the membrane, which is responsible for the sudden transient change in resistance and the increase of permeability to sodium. Without knowledge of the molecular forces controlling the ionic movements and thereby generating the bioelectric potentials, the mechanism cannot be understood. The difficulty of identifying the chemical reactions involved is readily recognized if two