DIFFUSION-THEORY, THE CELL AND THE SYNAPSE

The possibility exists that the cell internum is Ear more highly organ ised right down to the molecular level than was hitherto appreciated, to the point where ideas of a relatively solid-state chemistry model h ave been entertained (Coulson, R.A., 1993. The flow theory of enzyme k inetics-a role of solid geometry in the control reaction velocity in l ive animals. Int. J. Biochem. 25, 1445-1474). This contrasts sharply w ith the traditional dogma that diffusion is the mechanism by which mol ecules interact within an aqueous solution of the cell internum, altho ugh it should have been clear from an early stage that diffusion could not play other than a very resticted role in metabolic regulation. Wh en physicists began to question certain aspects of the fundamental Law of Heat Conductance formulated over 170 years ago by Fourier, Diffusi on Theory was also implicated (Maddox, J., 1989. Heat conductance is a can of worms. Nature 338, 373), and application of Fick's Laws of Dif fusion to living systems criticised (Agutter P.S., Malone, P.C., Wheat ley, D.N., 1995. Intracellular transport mechanisms: a critique of dif fusion theory. J. Theoret. Biol. 176, 261-272). While we have argued ( Wheatley, D.N., Malone, P.C., 1993. Heat conductance, diffusion theory and intracellular metabolic regulation. Biol. Cell 79: 1-5) that diff usion cannot be prevented from occurring, we found that, irrespective of whether it was a valid theory, diffusion was of little relevance in most actively metabolising cell systems. However, diffusion is still perceived as essential for interacting molecules to demonstrate their specificities. Any new model of the internal state of the living cell has to resolve this dilemma. The question also relates to molecular mo vement and ligand-receptor interactions outside the cell. In looking a t this situation, attention was paid to one site in the body in which diffusion has long been assumed to be essential, namely in the passage of the chemical transmitter between one neurone and the next across t he synaptic cleft. A detailed examination of this assumption has helpe d to identify one possible place in which the importance of diffusion over a distance of no more than 20-30 nm occurs, although objections t o diffusion being involved have been raised. The outcome, however, onl y re-enforces the conviction that diffusion has little role in metabol ic activity and is normally 'assisted' in almost all aspects of cell p hysiology. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.