Modulation of ion channels in rat neurons by the constituents of Hypericumperforatum

Despite almost forty years of widespread use of antidepressant drugs, their mode of action is still unknown. Hyperforin, a phloroglucinol derivative, is a major pharmacologically and therapeutically active constituent of Hype ricum perforatum extract that is widely used as an herbal antidepressant dr ug. However, the mechanism or mechanisms of action of these naturally abund ant, non-toxic extracts remain unclear. Enzymatically isolated patch-clampe d rat central and peripheral neurons exposed to rapid changes in the compos ition of external medium (concentration clamp) were used in our experiments to investigate the modulation of the various voltage- and ligand-gated cha nnels by hyperforin, as well as by other constituents of Hypericum perforat um. At nanomolar concentrations, hyperforin induced significant inhibition of various ion channels. in the case of P-type Ca2+ channels, we establishe d that hyperforin acts via interaction with calmodulin or through calmoduli n-activated pathways involving at least one second messenger. The results p resented here indicate that multiple mechanisms and extract constituents ma y be involved in the antidepressant action of Hypericum extracts, and that they could also possess neuroprotective and analgesic effects.