A transistor model for sodium flux across axonal membranes: evaluation of prediction criteria

The most remarkable properties of sodium flux across axonal membranes include the very high flux rate, the distinct selectivity for sodium, and the very tight and delicately timed change of ion permeability upon an electrical stimulus. Water-filled channels, such as they exist in gramicidine, may easily account for ion flux, yet gating would have to operate through allosteric changes that convey the signal to the channel proper. Upon elucidation of the sequence of the protein catalyzing sodium flux in electric eel (Noda et al., 1984), several models have been advanced that were based on identifying channel lining elements. An alternative model (Rosenbusch, 1987) viewed sodium flux and its regulation in analogy to a field effect transistor (FET), in which a gating current (GATE) causes a drastic change in permeability such that sodium ions flow downwards their electrochemical gradient from the outside (SOURCE) to the cytoplasm (DRAIN). The sequence of the protein was therefore scrutinized for the existence of elements potentially involved in this hypothetical concept. An examination showed that a structure representing an ion lattice in the core of the protein may exist, although the criteria applied were very different from those generally adopted for the prediction of membrane protein structure. The justification as well as the significance attached to such various criteria will, of course, only be resolved once the high resolution structure will be available. Yet, as ion flux across membrane proteins is fundamental to most living processes, it appears worthwhile to examine critically the mechanisms that may differ from those most widely adopted.