Abstract
The effect of 4-aminopyridine on [3H]acetylcholine release was studied in rat cerebral cortical synaptosomes in the presence of a several secretagogues that have different mechanisms of action. As found previously, 4-aminopyridine increased [3H]acetylcholine release in a concentration-dependent manner (5–10 mM); a high concentration (10 mM) also elevated [3H]choline efflux. However, the 35 mM K+ induced release of [3H]acetylcholine was attenuated by 4-aminopyridine at concentrations (less than 5 mM) that had no effect on transmitter release. At no concentration of 4-aminopyridine was the release of transmitter additive with 35 mM K+ induced release. Veratridine-induced release was neither attenuated nor additive with low concentrations of 4-aminopyridine, even when a sub-maximal concentration of the sodium ionophore was used (10 μM). In contrast, A23187-induced release was additive with that caused by 4-aminopyridine. These results suggest that: 1) 4-aminopyridine blocks potassium channels involved in regulating membrane potential in isolated cholinergic terminals; and 2) changes in the activity of these 4-aminopyridine sensitive K+ channels are not important in the nerve terminal's response to depolarization caused by sodium influx.
Similar content being viewed by others
References
Bartus, R. T., Dean, R. L., Beer, B., and Lippa, A. S. 1982. The cholinergic hypothesis of geriatric memory dysfunction. Science 217:408–414.
Bradford, M. 1976. A new technique for the, determination of protein in small samples. Anal. Biochem. 72:248–254.
Catterall, W. A. 1975. Activation of the action potential sodium ionophore of cultured neuroblastoma cells by veratridine and batrachotoxin. J. Biol. Chem. 250:4053–4059.
Cooper, J. R., and Meyer, E. M. 1982. Interrelationship between ACh release from synaptosomes and Na-K ATPase activity. Pages 521–531,in Pepeu, G., and Ladinsky, H. (eds.), Cholinergic Mechanisms, Plenum Press, New York.
Cooper, J. R., and Meyer, E. M. 1982. Relationship between Na-K ATPase activity and acetylcholine release in rat brain synaptosomes. Pages 521–530,in Pepeu, G., and Ladinsky, H., (eds.), Advances in Behavioral Biology, Vol. 25, Cholinergic Mechanisms, Plenum Press, New York.
Crews, F. T., Meyer, E. M., Gonzales, R. A., Otero, D. H., and Larsen, K. Presynaptic and postsynaptic approaches to enhance central cholinergic neutransmission. In: Treatment and Development Strategies for Alzheimer's Disease, in press.
Dolezal, V., and Tucek, S. 1983. The effects of 4-aminopyridine and tetrodotoxin on the release of acetylcholine from rat striatal slices. Naunyn-Schmiedeberg's Arch. Pharmacol. 323:90–95.
Loffelholz, K., and Weide, W. 1982. Aminopyridine and the release of acetylcholine. Trends Pharmacol. Sci. 3:147–149.
Meyer, E. M., and Cooper, J. R. 1981. Correlations between acetylcholine release and Na+, K+-ATPase activity in rat cortical synaptosomes. J. Neurochem. 36:467–475.
Meyer, E. M., St. Onge, E., and Crews, F. T. 1984. Effects of aging on the synaptosomal release of acetylcholine and its muscarinic modulation. Neurobiol. Aging 5:315–319.
Meyer, E. M., Crews, F. T., Otero, D. H., and Larsen, K. 1986. Aging decreases the sensitivity of rat cortical synaptosomes to calcium ionophore induced acetylcholine release. J. Neurochem. 47:1244–1246.
Meyer, E. M., and Otero, D. H. 1985. Pharmacological and ionic characterizations of the muscarinic receptors modulating [3H]acetylcholine release from rat cortical synaptosomes. J. Neurosci. 5:1202–1207.
Peterson, C., and Gibson, G. E. 1983. Aging and 3,4 diaminopyridine alter synaptosomal calicum uptake. J. Biol. Chem. 258:114821–114826.
St. Onge, E., Otero, D. H., Bottiglieri, D., and Meyer, E. M. 1986. Effects of several membrane channels and intracellular messengers on the muscarinic modulation of acetylcholine release. Neurochem. Res. 11:1547–1556.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Meyer, E.M., Otero, D.H. Differential effects of 4-aminopyridine on acetylcholine release triggered by K+ depolarization, veratridine, or A23187 in rat cerebral cortical synaptosomes. Neurochem Res 14, 157–160 (1989). https://doi.org/10.1007/BF00969632
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00969632