ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: The effect of ouabain and dihydroouabain on Na+-K+ ATPase, 86Rb uptake and the release of [14C]ACh (acetylcholine) from synaptosomal preparations of guinea pigs was compared. At low concentrations of glycoside (〈50 μm) there was a good correlation between the potency of ouabain and of dihydroouabain in inhibiting Na+-K+ ATPase and in causing the release of [l4C]ACh in a nondepolarising medium. Ouabain (200 μM) increased the release of [14C]ACh evoked by 25 mm-KCl, but not that evoked by 100μm-veratrine. The enhancement of release was independent of the presence of calcium. It was observed that in addition to [14C]ACh release, choline efflux was also stimulated by ouabain, independently of the presence of Ca2+. Experiments with hemicholinium-3 showed that the ouabain-induced increase in choline efflux was not due to an inhibition of reuptake. The effect of ouabain on intrasynaptosomal K+ concentration was measured in order to investigate the degree of depolarisation it caused. The decrease in K+ was found to be similar in magnitude and time course to that caused by veratrine. It was shown that ouabain-induced depolarisation caused an increased efflux of another positive ion (dibenzyldimethylammonium chloride) and retention of a negatively charged ion (chloride), as would be expected from the operation of the electrochemical potential gradient changing as a result of depolarisation. It is suggested that ouabain acts to stimulate ACh release from synaptosomes as follows: following blockage of the Na+-K+ ATPase there is rapid depolarisation which, if Ca2+ is present, provokes the normal Ca2+-dependent transmitter release process to occur. In addition, depolarisation accelerates the leakage of positive ions down their electrochemical potential gradient, but causes a retention of negative ions. Such an action does not depend on the presence of Ca2+, nor is it specific to transmitters.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1981.tb06316.x
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