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 greater than out), a Na+ gradient (out greater than 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 Km 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 microM) 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+.
Reith
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Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, New York, NY 10035.
Zimanyi
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O'Reilly
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D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D002712:Chlorides / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011188:Potassium / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D014634:Valinomycin / Q000494:pharmacology
D002712:Chlorides; D014634:Valinomycin; D012701:Serotonin; D012964:Sodium; D011188:Potassium