The endogenous alkaloid harmane: Acidifying and activity-reducing effects on hippocampal neurons in vitro

Abstract

Rationale The endogenous alkaloid harmane is enriched in plasma of patients with neurodegenerative or addictive disorders. As harmane affects neuronal activity and viability and because both parameters are strongly influenced by intracellular pH (pH i), we tested whether effects of harmane are correlated with altered pH i regulation. Methods and results Pyramidal neurons in the CA3 field of hippocampal slices were investigated under bicarbonate-buffered conditions. Harmane (50 and 100 μM) reversibly decreased spontaneous firing of action potentials and caffeine-induced bursting of CA3 neurons. In parallel experiments, 50 and 100 μM harmane evoked a neuronal acidification of 0.12 ± 0.08 and 0.18 ± 0.07 pH units, respectively. Recovery from intracellular acidification subsequent to an ammonium prepulse was also impaired, suggesting an inhibition of transmembrane acid extrusion by harmane. Conclusion Harmane may modulate neuronal functions via altered pH i-regulation. Implications of these findings for neuronal survival are discussed.