Efflux of 5-HIAA from 5-HT neurons: a membrane potential-dependent process

The effect of the membrane potential on the efflux of 5-HIAA from 5-HT neurons was studied in anesthetized (halothane: 1% in gas mixture of N2O: 70% and O2: 30%) cats. The endogenous 5-HT and its metabolite 5-HIAA were measured continuously from the cortex, the thalamus, the hypothalamus and the raphe nuclei using brain microdialysis technique combined with HPLC-ED monoamine measurements. Membrane potential variations were induced by changing the extracellular concentration of potassium through the microdialysis membrane. The levels of the extracellular 5-HIAA varied according to the different regions of the brain, being highest in the hypothalamus and lowest in the cerebral cortex. Increases in the extracellular potassium from 4 to 120 mM invariably produced a decrease of the extracellular 5-HIAA in all the tested brain regions. This decrease was inversely proportional to the logarithm of extracellular potassium concentration. Thus, it is postulated that the 5-HIAA is moved from inside the cell to extracellular space by an active mechanism of transport electrically coupled to the membrane potential.