The endogenous alkaloid harmane: acidifying and activity-reducing effects on hippocampal neurons in vitro.
BACKGROUND
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.


RESULTS
Pyramidal neurons in the CA3 field of hippocampal slices were investigated under bicarbonate-buffered conditions. Harmane (50 and 100 microM) reversibly decreased spontaneous firing of action potentials and caffeine-induced bursting of CA3 neurons. In parallel experiments, 50 and 100 microM 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.


CONCLUSIONS
Harmane may modulate neuronal functions via altered pH(i)-regulation. Implications of these findings for neuronal survival are discussed.
Bonnet
Udo
U
Department of Addictive Behaviour and Addiction Medicine, University of Duisburg/Essen, Virchowstr. 174, D-45147 Essen, Germany. udo.bonnet@uni-due.de
Scherbaum
Norbert
N
Wiemann
Martin
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D006168:Guinea Pigs; D006247:Harmine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D023421:Models, Animal; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism
D000470:Alkaloids; D002110:Caffeine; D006247:Harmine; C005010:harman