On the mechanism by which extracellular sodium depletion causes 5-hydroxytryptamine release from rat brain...

The release of 3H-labelled 5-hydroxytryptamine (5-HT) from preloaded and superfused rat forebrain synaptosomes in response to extracellular Na+ depletion was studied. In the absence of monoamine oxidase inhibitors, the release of [3H]-5-HT caused by Na+ depletion was not affected by immobilizers of the plasma membrane 5-HT carrier. The release of [3H]-5-HT in response to Na+ depletion was also either independent of, or inversely related to the concentration of extracellular Ca2+ depending on the degree to which extracellular Na+ was reduced. The efflux of 45Ca2+ from prelabelled synaptosomes was decreased by Na+ reduction but the amplitude of the changes in 45Ca2+ efflux did not totally correlate with the changes in [3H]-5-HT efflux under the same experimental conditions. These results suggest that the release of [3H]-5-HT caused by Na+ depletion in drug-free synaptosomes is not mediated by 5-HT efflux through the plasma membrane carrier, nor to changes in cytosolic Ca2+ consequent to changes in Ca2+ fluxes across the plasma membrane. The results have been tentatively explained as an elevation of spontaneous 5-HT efflux caused by an increase in membrane fluidity mediated by the ionic manipulations used to produce the Na+-depleted media.