ABSTRACT
But how could a cell surrounded by a lipid membrane produce a voltage? In 1889 Nernst published his famous equation relating voltage and ion concentration. e concept that a voltage could result from an ion concentration dierence was used by Bernstein in his famous hypothesis of 1902. Muscle cells, and, in fact, all cells have high internal K+ concentration, and are bathed in extracellular uid that has a low concentration of K+ and a high concentration of Na+. Bernstein postulated that in the resting state, the membrane of a muscle cell is predominantly permeable to K+, resulting in a negative internal voltage in accordance with Nernst’s equation. e selective K+ permeability, he postulated, was lost when an action potential swept over the ber, changing the membrane voltage to near zero. (In fact, he recorded an overshoot in the potential change, but seems not to have appreciated its signicance.)
In the 1930s J.Z. Young brought to the attention of K.S. Cole a very large axon, the giant axon of the squid, the preparation crucial to solving the mechanism of the nerve impulse. is giant
axon is large enough (up to 1 mm diameter) that electrodes can be carefully threaded inside, allowing Cole and collaborators to measure directly the axon’s membrane voltage (Vm), which they found to be approximately −60 mV inside at rest. Many other important ndings and inventions followed from Cole’s lab. During an action potential Vm was found to go well beyond 0 mV, that is, it overshot the value expected from Bernstein. Slightly before and during the action potential, membrane conductance (or permeability) was found to increase. Marmont (1949), in Cole’s lab, introduced the very important space clamp: a wire was threaded into the axon, lowering its internal longitudinal resistance to the point that a several centimeter length of axon was made isopotential, and behaved electrically like a single large patch of membrane. Two very important contributions of the Cole lab were the current clamp (Marmont) and the voltage clamp (Cole, 1949; Marmont, 1949).
