Neurochemical Research

, Volume 9, Issue 6, pp 815–821 | Cite as

Role of synaptosomal Na-accumulation in transmitter release

  • Edwin M. Meyer
  • Jack R. Cooper
Original Articles


The mechanism whereby Na+, K+-ATPase inhibitors such as ouabain trigger transmitter release in a calcium-independent manner remains obscure. We have examined the possible role of intra-synaptosomal sodium ion accumulation in ouabain-induced acetylcholine (ACh) release by: 1) Measuring22Na accumulation in cat cortical synaptosomes in the presence of ouabain, A23187, veratridine, or strophanthidin over the same time course in which we previously determined their effects on ACh release; and 2) measuring synaptosomal22Na accumulation and ACh-release in the presence of ouabain plus tetrodotoxin in normal or calcium-free buffer. Our results indicate that tetrodotoxin-dependent22Na accumulation is at least partially responsible for ouabain-induced ACh release in normal and calcium-free media, but that this ion-accumulation per se is not sufficient to elicit release with other secretogogues.


Sodium Acetylcholine Ouabain A23187 Transmitter Release 
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  1. 1.
    Schwartz, A., Lindenmayer, G. E., andAllen, J. C., 1975. Sodium-potassium adenosine triphosphatase-pharmacological, physiological, and biochemical aspects. Pharmacol. Rev. 27:3–134.PubMedGoogle Scholar
  2. 2.
    Sweadner, K. J., 1979. Two molecular forms of Na+, K+-ATPase in brain. J. Biol. Chem. 254:6060–6067.PubMedGoogle Scholar
  3. 3.
    Meyer, E. M., andCooper, J. R. 1981. Correlations between ACh release and Na+, K+-ATPase activity. J. Neurochem. 36:467–478.PubMedGoogle Scholar
  4. 4.
    Vizi, E. S. 1978. Na+, K+-Activated adenosinetriphosphatase as a trigger in transmitter release. Neuroscience 3:367–384.PubMedGoogle Scholar
  5. 5.
    Paton, W. D. M., Vizi, E. S., andAboo Zar, M. 1971. Mechanism of acetylcholine release from parasympathetic nerves. J. Physiol. (Lond.) 215:819–833.Google Scholar
  6. 6.
    Garcia, A. G., andKirpekar, S. M. 1975. Inhibition of Na, K-activated ATPase and release of neurotransmitters. Nature 257:722.PubMedGoogle Scholar
  7. 7.
    Logan, J. G., andO'Donovan, D. I. 1976. Effects of ouabain and activation of neural membrane ATPase by biogenic amines. J. Neurochem. 27:185–189.PubMedGoogle Scholar
  8. 8.
    Vyas, S. andMarchbanks, R. M. 1981. The effect of ouabain on the release of [14C]acetylcholine and other substances from synaptosomes. J. Neurochem. 37:1467–1474.PubMedGoogle Scholar
  9. 9.
    Vizi, E. S. 1979. Presynaptic modulation of neurochemical transmission. Prog. Neurobiol. 12:181–290.PubMedGoogle Scholar
  10. 10.
    Kirpekar, S. M., Prat, I. C., andYamamoto, H. 1970. Effects of metabolic inhibitors on norepinephrine release from perfused spleen of cat. J. Pharmacol. Exp. Therap. 172:342–349.Google Scholar
  11. 11.
    Rutledge, C. O., 1978. Effect of metabolic inhibitors and ouabain on amphetamine-and potassium-induced release of biogenic amines from brain tissue. Biochem. Pharmacol. 27:511–516.PubMedGoogle Scholar
  12. 12.
    Donatsche, P., Lowe, D. A., Richardson, B. P., andTaylor, P., 1977. Functional significance of sodium channels in pancreatic beta cell membranes. J. Physiol. (Lond.) 267:357–376.Google Scholar
  13. 13.
    Ortiz, C. L. 1980. Intracellular sodium accumulation and transmitter release at crustacean neuromuscular junctions. Fed. Proc. 39:1524–1526.PubMedGoogle Scholar
  14. 14.
    Rahamimoff, R., Erulkar, S. D., Alnaes, E., Rotshenker, S., andRahamimoff, H. 1976. Modulation of transmitter release by calcium ions and nerve impulses. Cold Spring Harbor Symposium Quant. Biol. 40:107–116.Google Scholar
  15. 15.
    Sgaragli, G. P., Sen, I., Baba, A., Schulz, R. A., andCooper, J. R., 1977. The mechanisms of action of collagenase on the inhibition of release of acetylcholine from synaptosomal preparations. Brain Res. 134:113–123.PubMedGoogle Scholar
  16. 16.
    Nemeth, E. F., andCooper, J. R. 1978. Effect of somatostatin on acetylcholine release from rat hippocampal synaptosomes. Brain Res. 165:166–170.Google Scholar
  17. 17.
    Bradford, M. 1976. Rapid and sensitive method for quantitation of microgram quantities of protein using principle of protein-dye binding. Anal. Biochem. 72:248–254.PubMedGoogle Scholar
  18. 18.
    Ling, C-M., andAbdel-Latif, A. A. 1968. Studies on sodium transport in rat brain nerve particles. J. Neurochem. 15:721–728.Google Scholar
  19. 19.
    Blaustein, M. P., andGoldring, J. M., 1975. Membrane potentials in pinched-off presynaptic nerve terminals monitored with a fluorescent probe-evidence that synaptosomes have potassium diffusion potentials. J. Physiol. (Lond.) 247:589–615.Google Scholar
  20. 20.
    Abita, J.-P., Chicheportiche, R., Schweitz, H., andLazdunski, M., 1977. Effects of neurotoxins (veratridine, sea-anemone toxin, tetrodotoxin) on transmitter accumulation and release by nerve-terminals in vitro. Biochemistry 16:1838–1844.PubMedGoogle Scholar
  21. 21.
    Akerman, K. E. O., andNicholls, D. G., 1981. Calcium transport by intact synaptosomes. Influence of A23187 on plasma-membrane potential, plasma-membrane calcium transport, mitochondrial membrane potential, respiration, cytosolic free-calcium concentration, and noradrenaline release. Eur. J. Biochem. 115:67–73.PubMedGoogle Scholar
  22. 22.
    Matsuda, T., andCooper, J. R., 1983. Inhibition of neuronal sodium and potassium ion activated adenosine triphosphatase by pyrithiamin. Biochemistry 22:2209–2213.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1984

Authors and Affiliations

  • Edwin M. Meyer
    • 1
  • Jack R. Cooper
    • 1
  1. 1.Department of PharmacologyYale University School of MedicineNew Haven

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