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- Title
The TRPC6 channel activator hyperforin induces the release of zinc and calcium from mitochondria.
- Authors
Tu, Peng; Gibon, Julien; Bouron, Alexandre
- Abstract
Hyperforin, an extract of the medicinal plant hypericum perforatum (also named St John’s wort), possesses antidepressant properties. Recent data showed that it elevates the intracellular concentration of Ca2+ by activating diacylglycerol-sensitive C-class of transient receptor potential (TRPC6) channels without activating the other isoforms (TRPC1, TRPC3, TRPC4, TRPC5, and TRPC7). This study was undertaken to further characterize the cellular neuronal responses induced by hyperforin. Experiments conducted on cortical neurons in primary culture and loaded with fluorescent probes for Ca2+ (Fluo-4) and Zn2+ (FluoZin-3) showed that it not only controls the activity of plasma membrane channels but it also mobilizes these two cations from internal pools. Experiments conducted on isolated brain mitochondria indicated that hyperforin, like the inhibitor of oxidative phosphorylation, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), collapses the mitochondrial membrane potential. Furthermore, it promotes the release of Ca2+ and Zn2+ from these organelles via a ruthenium red-sensitive transporter. In fact, hyperforin exerts complex actions on CNS neurons. This antidepressant not only triggers the entry of cations via plasma membrane TRPC6 channels but it displays protonophore-like properties. As hyperforin is now use to probe the functions of native TRPC6 channels, our data indicate that caution is required when interpreting results obtained with this antidepressant.
- Subjects
HYPERICUM perforatum; ANTIDEPRESSANTS; ZINC; CALCIUM; MITOCHONDRIA; USEFUL plants
- Publication
Journal of Neurochemistry, 2010, Vol 112, Issue 1, p204
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2009.06446.x