Neurochemical Research

, Volume 18, Issue 8, pp 927–936 | Cite as

A model of the sodium dependence of dopamine uptake in rat striatal synaptosomes

  • D. D. Wheeler
  • A. M. Edwards
  • B. M. Chapman
  • J. G. Ondo
Original Articles


Initial velocity of uptake of dopamine (DA) has been measured in rat striatal synaptosomes as a function of both [DA] and [Na]. Carrier mediated uptake is totally dependent on external sodium. The data were fitted to a rapid equilibrium model which has been found in previous studies to fit, with appropriate simplification, uptake data for glutamate, GABA, and choline in several brain regions under varying conditions. This model also gives a good fit to the dopamine data. The minimal best fit simplification of this model allows for DA uptake along with two sodium ions and predicts that apparent maximal velocity of uptake should increase with [Na], while the Michaelis-Menten constant should decrease. The minimal best fit model for DA, and a number of kinetic parameters which quantitate the model, are compared to those for the GABA, glutamate, and choline transporters. The results are consistent with a symmetrical, rapid equilibrium model, which has been presented previously for other neurotransmitters and precursors (18). This model offers a unifying basis for understanding the sodium and membrane potential dependence of neurotransmitter transport and the possible participation of transporters in depolarization induced release throughout the CNS.

Key Words

Dopamine uptake synaptosomes sodium dependence 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Schultz, S. G., and Curran, P. 1970. Coupled transport of sodium and organic solutes. Physiol. Rev., 50:637–718.Google Scholar
  2. 2.
    Hopfer, U., and Gloseclose, R. 1980. The mechanism of Na+-dependent D-glucose transport. J. Biol. Chem., 255:4453–4462.Google Scholar
  3. 3.
    Kanner, B. I. 1983. Bioenergetics of neurotransmitter transport. Biochem. Biophys. Acta, 726:293–316.Google Scholar
  4. 4.
    Wheeler, D. D., and Boyarsky, L. L., 1967. Glutamic acid uptake in peripheral nerve. Fed. Proc., 26:766.Google Scholar
  5. 5.
    Wheeler, D. D. and Boyarsky, L. L. 1968. Influx of glutamic acid in peripheral nerve. Characteristics of influx. J. Neurochem., 15:1019–1031.Google Scholar
  6. 6.
    Wheeler, D. D., and Boyarsky, L. L. 1971. Influx of glutamic acid in peripheral nerve. Energy, ionic, and pH dependence. J. Neurobiol., 2:181–190.Google Scholar
  7. 7.
    Wheeler, D. D., and Graves, J. S. 1983. A model of the sodium and membrane potential dependence of high affinity glutamic acid transport in cortical synaptosomes. J. Theoret. Neurobiol., 2:1–22.Google Scholar
  8. 8.
    Hurd, Y. L., and Ungerstedt, U. 1989. Influence of a carrier transport process onin vivo release and metabolism of dopamine: dependence on extracellular Na+. Life Sci., 45:283–293.Google Scholar
  9. 9.
    Snyder, S. H., M. J. Kuhar, A. I. Green, J. T. Coyle, and Shaskan, E. 1970. Uptake and subcellular localization of neurotransmitters in the brain. Intern. Rev. Neurobiol., 13:127–158.Google Scholar
  10. 10.
    Iversen, L. L. 1971. Role of transmitter uptake mechanisms in synaptic neurotransmission. Br. J. Pharmacol., 41:571–591.Google Scholar
  11. 11.
    Iversen, L. L., 1973. Catecholamine uptake processes. Brit. Med. Bull., 29:130–135.Google Scholar
  12. 12.
    Krnjevic, K. 1974. Chemical nature of synaptic transmission in vertebrates. Physiol. Rev., 54:418–540.Google Scholar
  13. 13.
    Kuhar, M. J., and Murrin, L. C. 1978. Sodium-dependent, high affinity choline uptake. J. Neurochem., 30:15–21.Google Scholar
  14. 14.
    Wheeler, D. D. 1979. A model of high affinity choline transport in rat cortical synaptosomes. J. Neurochem., 32:1197–1213.Google Scholar
  15. 15.
    Balcar, V. J., and Johnston, G. A. R. 1973. High affinity uptake of transmitters: Studies on the uptake of L-aspartate, GABA, L-glutamate, and glycine in cat spinal cord. J. Neurochem., 20:529–539.Google Scholar
  16. 16.
    Wheeler, D. D. 1980. A model for GABA and glutamic acid transport by cortical synaptosomes. Pharmacol., 21:141–152.Google Scholar
  17. 17.
    Bennett, J. P. Jr., W. J. Logan, and Snyder, S. H. 1973. Amino acids as central nervous transmitters: The influence of ions, amino acid analogues, and ontogeny on transport systems for L-glutamic and L-aspartic acids and glycine into central nervous synaptosomes of the rat. J. Neurochem., 21:1533–1550.Google Scholar
  18. 18.
    Wheeler, D. D. 1987. Are there both low and high affinity glutamate transporters in rat cortical synaptosomes? Neurochem. Res., 8:667–680.Google Scholar
  19. 19.
    Kuhar, M. J., Sanchez-Roa, P. M., Wong, D. F., Dannals, R. F., Grigoriadis, D. E., Lew, R., and Milberger, M. 1990. Dopamine transporter: biochemistry, pharmacology and imaging. Eur. Neurol., 30 (suppl I):15–20.Google Scholar
  20. 20.
    Horn, A. S. 1978. Characteristics of neuronal dopamine uptake. Adv. Biochem. Psychopharmacol., 19:25–34.Google Scholar
  21. 21.
    Krueger, B. K. 1990. Kinetics and block of Dopamine uptake in synaptosomes from rat caudate nucleus. J. Neurochem., 55:260–267.Google Scholar
  22. 22.
    Wheeler, D. D., Chapman, B. M., and Ondo, J. G. 1993. Effects of veratridine and cocaine on the kinetics of synaptosomal dopamine release. Pharmacol., (in press).Google Scholar
  23. 23.
    Collings, T. A., Braid, H. L., Greene, W. B., and Wheeler, D. D. 1986. Morphometric and autoradiographic analysis of crude synaptosomal preparations from rat cerebral cortex. Neurochem. Res., 11:707–721.Google Scholar
  24. 24.
    Nelder, J. A., and Mead, R. 1965. A simplex method for function minimization. Comput. J., 7:308–315.Google Scholar
  25. 25.
    Wheeler, D. D. 1981. A model of GABA transport by rat cortical synaptosomes: further studies. J. Theoret. Neurobiol., 1:43–59.Google Scholar
  26. 26.
    Wheeler, D. D. 1983. Aging of the high affinity GABA transporter in synaptosomes from the hypothalamus of the rat. Exp. Geront., 18:125–135.Google Scholar
  27. 27.
    Wheeler, D. D. 1984. The effect of membrane potential on initial velocity of GABA uptake and steady state distribution ratio in rat cortical synaptosomes. Neurochem. Res., 9:649–660.Google Scholar
  28. 28.
    Wheeler, D. D., and Wise, W. C. 1983. A kinetic analysis of the release of acidic amino acids from rat cortical synaptosomes. Neurochem. Res., 8:1111–1134.Google Scholar
  29. 29.
    Wheeler, D. D. 1984. Kinetics of D-aspartic acid release from rat cortical synaptosomes. Neurochem. Res., 9:1599–1614.Google Scholar

Copyright information

© Plenum Publishing Corporation 1993

Authors and Affiliations

  • D. D. Wheeler
    • 1
  • A. M. Edwards
    • 1
  • B. M. Chapman
    • 1
  • J. G. Ondo
    • 1
  1. 1.Department of PhysiologyMedical University of South CarolinaCharleston

Personalised recommendations