Voltage-Gated Ion Channels and Electrical Excitability

showed that local circuit currents from an excited region Our ability todo gymnastics, to perceive a colorful world, of nerve are needed to bring the next region into activity. and to process language relies on rapid communication This meant that depolarization is the natural stimulus among neurons. Such signaling, the fastest in our bodfor action potential propagation. J. Z. Young (1936) reies, involves electrical messages produced as ion chandiscovered the giant axon of the squid. It provided the nels in cell membranes open and close. Various ion first convenient way to place electrodes and even elecchannels mediate sensory transduction, electrical “comtrode arrays inside an excitable cell. Cole and Curtis putations,” propagation over longdistances, and synap(1939) showed that the membrane of the squid giant tic transmission. Here, we focus on voltage-gated ion axon increases its conductance 40-fold during an action channels, the family of channels that includes the familpotential, in apparent agreement with Bernstein’s earlier iar Na, K, and Ca channels of nerve and muscle theory of membrane breakdown. Hodgkin and Huxley excitability. In the computer metaphor of the brain, the (1939) discovered with intracellular electrodes that the voltage-gated ion channels are like the transistors of peak of theaction potential overshoots 0 mV by a signifilogical circuits, detecting, amplifying, and reshaping cant margin. The overshoot was a serious problem for electrical messages. Our basic understanding of these the Bernstein theory, and Hodgkin and Katz (1949) evenproteins maintains the framework and rigor established tually provided the crucial resolution: the overshoot is 50 years ago by Hodgkin and Huxley (1952), enriched by determined by the Na equilibrium potential and must much new molecular information and by insights gained be due to Na entry during the action potential. from patch-clamp methods. With this background, Hodgkin and Huxley sought to Although we have had full amino acid sequences of understand how excitation regulates the entry of Na voltage-gated channels for over a decade, we still lack ions. They developed the voltage clamp to measure even modest resolution three-dimensional information. ion movements as electric currents. The clamp records All three-dimensional diagrams in the literature derive revealed an inward current followed by an outward cur-