Roderick MacKinnon - Nobel Lecture

All living cells are surrounded by a thin, approximately 40 Å thick lipid bilayer called the cell membrane. The cell membrane holds the contents of a cell in one place so that the chemistry of life can occur, but it is a barrier to the movement of certain essential ingredients including the ions Na+, K+, Ca2+ and Cl-. The barrier to ion flow across the membrane – known as the dielectric barrier – can be understood at an intuitive level: the cell membrane interior is an oily substance and ions are more stable in water than in oil. The energetic preference of an ion for water arises from the electric field around the ion and its interaction with neighboring molecules. Water is an electrically polarizable substance, which means that its molecules rearrange in an ion’s electric field, pointing negative oxygen atoms in the direction of cations and positive hydrogen atoms toward anions. These electrically stabilizing interactions are much weaker in a less polarizable substance such as oil. Thus, an ion will tend to stay in the water on either side of a cell membrane rather than enter and cross the membrane. And yet numerous cellular processes, ranging from electrolyte transport across epithelia to electrical signal production in neurons, depend on the flow of ions across the membrane. To mediate the flow, specific protein catalysts known as ion channels exist in the cell membrane. Ion channels exhibit the following three essential properties: (1) they conduct ions rapidly, (2) many ion channels are highly selective, meaning only certain ion species flow while others are excluded, (3) their function is regulated by processes known as gating, that is, ion conduction is turned on and off in response to specific environmental stimuli. Figure 1 summarizes these properties (figure 1). The modern history of ion channels began in 1952 when Hodgkin and Huxley published their seminal papers on the theory of the action potential in the squid giant axon (Hodgkin and Huxley, 1952a; Hodgkin and Huxley, 1952b; Hodgkin and Huxley, 1952c; Hodgkin and Huxley, 1952d). A fundamental element of their theory was that the axon membrane undergoes changes in its permeability to Na+ and K+ ions. The Hodgkin-Huxley theory