Surmounting barriers in ionic channels

Abstract

Biological cells are defined by the membrane that shields their vital molecules from the environment. The lipid bilayer of the membrane is an effective dielectric shield (Parsegian, 1969; Andersen, 1978; Honiget al.1986), preventing penetration by charged molecules: the lipid presents a large electrostatic energy barrier because it cannot neutralize the charge of solute molecules nearly as well as water. This energy barrier inhibits the permeation of solutes with local charge, even metabolites. Of course, metabolites do enter cells, and so physiologists have suspected (for a very long time, Hille, 1984, ch. 8) that the membrane shield is pierced by aqueous channels, through which solutes diffuse (with their local charge substantially neutralized) as they cross the membrane. These aqueous pores now have molecular reality (e.g. Nodaet al.1984; Miller, 1986). Each is formed by a specialized protein, integral to membranes, perhaps shaped like a thick-walled pipe, called ionic channels. Channels control the movement of many important molecules in and out of cells by the ‘gating’ mechanism that controls their opening and closing and by the selective properties of their open channel.