The overshoot phenomenon in cotransport.

Based on simplified equations, the overshoot curve experimentally observed with Na+-linked cotransport of neutral substrate (sugars or amino acids) has been simulated by computer. The approach is in principle similar to that of previous approaches (Weiss, S.D., McNamara, P.D. and Segal, S. (1981) J. Theor. Biol. 91, 597-608), but more general; in particular, it includes the effect of electrical membrane potential difference, and the quantitative relationship between height of peak and certain transport parameters, such as maximum rate, dissociation constant of ternary complex, electric charge of translocator, respectively. In addition, it tests two alternative models with respect to the rate-determining step: the translocation, on the one hand, and the association/dissociation of the ligands at the translocator site, on the other. The major findings are the following: (1) An overshoot can be obtained similar to that usually found experimentally, provided that maximum rate and affinity between translocator and transport of solute exceed certain minimum values. (2) The overshoot effect with Na-linked cotransport is enhanced by a negative membrane potential (inside relative to outside) and decreased by a positive potential. In the first case, the peak is higher and occurs faster. In the latter case, the peak is lower and delayed. (3) The effect of an electric potential difference on the overshoot curve does not depend appreciably on the charge of the empty translocator, except if the translocation of the latter is strongly rate-limiting. (4) To obtain an overshoot curve, it is not necessary that the translocation step be rate-limiting, contrary to what has been postulated previously (Läuger, P. (1980) J. Membrane Biol. 57, 163-178).