Ionic Channels in Biological Membranes

ABSRACT Ionic channels are proteins with holes down their middle that control access to biological cells and thus govern an enormous range of biological functions important in health and disease. A substantial fraction of the drugs used in clinical medicine act directly or indirectly on channels. Channels have a simple well defined structure, and the fundamental mechanism of ionic motion is known to be electrodiffusion. The current through individual channel molecules can easily be measured, and is in fact measured in hundreds if not thousands of laboratories everyday. Thus, ionic channels are ideal objects for physical investigation: on the one hand, they are well defined structures following simple physics, on the other hand they are of general biological importance. A simple theory of ion permeation through a channel is presented, in which diffusion occurs according to Fick's law and drift according to Ohm's law, in the electric field determined by all the charges present. This theory accounts for permeation in the channels studied to date in a wide range of solutions. Interestingly, the theory works because the shape of the electric field is a sensitive function of experimental conditions, e.g., ion concentration. Rate constants for flux are sensitive functions of ionic concentration because the fixed charge of the channel protein is shielded by the ions in an near it. Such shielding effects are not included in traditional theories of ionic channels, or other proteins, for that matter.