Gate Control of Ion Flux in Axons

This discussion deals with certain aspects of axon excitability in terms of the relation between molecular structure and function in the membrane, emphasizing the role of certain explicit assumptions in working out quantitative relations. The problem is formally to calculate the behavior of the axon membrane when exposed to electrical stimuli directly from the molecular structure of the membrane. Calculation of voltage clamp curves under a variety of conditions will suffice. The concept of the axon membrane as a simple diffusion medium is now known to be inadequate and among the ideas put forward for improving the interpretation of axon behavior are those involving carrier molecules, charged channels through the membrane, and surface layer control. It is, of course, possible that any or all of these are present in the membrane. However, current notions of the composition and arrangement of the bimolecular lipid layer encourage the exploration of the surface layer approach for excitation problems. Chemical, electron microscopical, and other data suggest the presence of an oriented bimolecular lipid layer roughly 100 A thick, coated with protein or other material on both sides, and protected by Schwann cells and connective tissue on the outside and by axoplasm on the inside. Attention is here directed to the bimolecular layer which contains phospholipids among other elements. These phospholipids have large moment, flexible dipoles at one end of long hydrocarbon chains, and the negative element of these dipoles is provided by partially substituted phosphate groups. Such dipoles are orientable in an electric field and the phosphate groups act as ion exchange sites whose specificity can be affected by their configuration. Thus, there are present in the membrane, molecular elements capable of providing control of ion flow by acting as gates operated by changes in the electric field. Explicit analysis of such a system permits calculation of current-voltage-time curves under voltage clamp conditions for relevant ions, provided of course that the details of the system are appropriately specified. In the absence of exact knowledge of the molecular structure and steric behavior, such specifications require assumptions to be made, explicit and simple, in order for the analysis to be carried through.