ABSTRACT

Using voltage-clamp on the membrane of a squid giant axon bathed in a solution with controlled ion concentrations, they concluded that at rest the membrane was predominantly selective to K+ resulting in a negative transmembrane potential (according to the electrophysiological convention, the transmembrane potential is measured inside the cell relative to the outside). On the other hand, Na+ was responsible for the inward current causing the cell membrane to become more positive than at rest, referred to as depolarization. Hodgkin and Huxley identied these two major ionic components responsible for the generation of the action potential in their seminal 1952 papers (Hodgkin and Huxley, 1952a,b,c,d; Hodgkin et al., 1952), and developed a model directly correlating Na+ and K+ uxes with excitation and electric conduction in the squid giant axon, earning them the Nobel Prize in 1963. ese studies informed the conclusion that nerve impulse propagation is an electrical process involving a delicate balance of ion uxes across the cell membrane controlled by the opening and closing (gating) of highly selective ion channels. Ion selectivity and regulated gating are crucial to generating the action potential.