MODEL OF HIGH-AFFINITY CHOLINE TRANSPORT IN RAT CORTICAL SYNAPTOSOMES

Abstract— Initial velocity of choline uptake by cortical synaptosomes from the Long‐Evans rat has been measured as a function of both choline and sodium concentration. These data were then fitted to the rate equation for each of several possible models which characterize the participation of sodium in the transport process, and the models giving best fit were identified. Although one cannot unequivocally distinguish between a model including a high affinity carrier component plus diffusion and one including both high affinity and low affinity carriers, the conclusions concerning the high affinity component are the same in both cases. The major conclusions from the model are as follows: (1) The carrier may first combine with either choline or sodium; if the first reaction is with sodium, then there is an obligatory reaction with a second sodium before choline can interact with the carrier. (2) Translocation may occur as either CS or CNa2S (C= carrier; S= choline; CS= carrier‐substrate complex). (3) The apparent maximal velocity (Va) is dependent on the sodium concentration. (4) K1, the choline concentration giving Va/2. is also dependent on the sodium concentration. K1 increases with [Na] from 0 to 38.41 mm; above 38.41 mm‐[Na]. K1 declines with [Na]. (5) There is a sigmoidal relationship between velocity of uptake and [Na]; however, uptake is not zero at [Na] = 0. (6) Jm. uptake at a given [choline] and infinite [Na]. is hyperbolically related to the choline concentration, but changes slowly over the range of 0.5–5.0 ± 10‐6m. (7) KNa, the sodium concentration giving a velocity equal to Jm/2, is related to the choline concentration by a quadratic equation, and was found to be greater than physiological [Na] at choline concentrations of 0.5, 0.6, or 1.0 ± 10‐6m. but less than physiological [Na] at choline concentrations of 2.0 or 5.0 ± 10‐6m. The best fit model for the high affinity uptake of choline is very similar to what has been found in previous studies for the high affinity uptake of glutamic acid and GABA, thus raising the question of whether or not all high affinity synaptosomal mechanisms may be variations of a common model. Copyright © 1979, Wiley Blackwell. All rights reserved