Role of ions and membrane potential in uptake of serotonin into plasma membrane vesicles from mouse brain

Plasma membrane vesicle preparations from mouse cerebral cortex actively accumulated [ 3H]serotonin upon the imposition of a K + gradient (in > out), a Na + gradient (out > in), and the presence of external Cl −. Maximal stimulation of uptake by internal K + occurred at 15 mM and half-maximal stimulation at 2 mM. Internal K + did not enhance uptake merely via generation of a membrane potential because simultaneous parallel increases in internal and external K + concentration also stimulated uptake. External Cl − increased serotonin uptake with a K m of 18 mM and a Hill number of 1.0, suggesting a requirement for one chloride ion for transport. Uptake could not be driven by internal H + instead of K +. Estimation of the membrane potential by the distribution of triphenylmethylphosphonium ion showed a modest effect of valinomycin (1–20 μM) in increasing the potential from −19 to −31 mV accompanied by an increase in serotonin uptake. Proton ionophores prevented this effect of valinomycin and, by themselves, reduced the potential to −6 mV, but did not affect serotonin transport. A model is proposed for serotonin transport in brain plasma membrane vesicles that is similar to the model for porcine blood platelet vesicles as far as electroneutrality and stimulation by K + Na +, and Cl − are concerned, but that is different in substitution of internal H + for K +.