Hyperforin attenuates various ionic conductance mechanisms in the isolatedhippocampal neurons of rat

Citation
S. Chatterjee et al., Hyperforin attenuates various ionic conductance mechanisms in the isolatedhippocampal neurons of rat, LIFE SCI, 65(22), 1999, pp. 2395-2405
Citations number
26
Categorie Soggetti
Biochemistry & Biophysics
Journal title
LIFE SCIENCES
ISSN journal
00243205 → ACNP
Volume
65
Issue
22
Year of publication
1999
Pages
2395 - 2405
Database
ISI
SICI code
0024-3205(19991022)65:22<2395:HAVICM>2.0.ZU;2-B
Abstract
Effects of hyperforin, an acylphloroglucinol derivative isolated from antid epressive medicinal herb Hypericum perforatum (St. John's Wort), on voltage - and ligand-gated ionic conductances were investigated. Whole-cell patch c lamp and concentration clamp techniques on acutely isolated hippocampal pyr amidal neurons and on cerebellar Purkinje neurons of rat were used. At conc entrations between 3 to 100 mu M hyperforin induced a dose and time depende nt inward current which completely stabilized within a few seconds. Althoug h 1 mu M hyperforin inhibited virtually all investigated conductances (GABA greater than or equal to I-Ca(N) > I-Na greater than or equal to I-Ca(P) g reater than or equal to AMPA greater than or equal to I-K(A) > NMDA > I-K(D R)), its effects on several of them could not be reversed by repeated washi ngs. Dose response studies revealed that although AMPA induced current is i nhibited by hyperforin in a competitive manner, these responses are not com pletely blocked by very high concentration of the agent. On the contrary, h owever, NMDA receptor-activated ionic conductance could be completely and u ncompetitively inhibited by the agent. Taken together these observation not only reconfirm that hyperforin is a major neuroactive component of hyperic um extracts but also demonstrate that this structurally unique and naturall y abundant molecule is a potent modulation of mechanism involved in the con trol of neuronal ionic conductances. Various observed effects of hyperforin do not, however, seem to be mediated by one single molecular mechanism of action of the agent.