title: Ginsenosides regulate ligand-gated ion channels from the outside.
abstract: Treatment with ginsenosides, the major active ingredients of Panax ginseng, produces a variety of physiological effects on the central and peripheral nervous systems. Ginsenosides inhibit various types of ligand-gated ion channel but it is not clear whether they act from within or outside the cell since they are somewhat membrane-permeable. In the present study, we used the Xenopus oocyte gene expression system to determine from which side of the cell membrane the ginsenoside Rg3 (Rg3), and M4, a ginsenoside metabolite, act to regulate ligand-gated ion channel activity. Ligand-gated ion currents were measured using the two-electrode voltage clamp technique. Rg3 and M4 inhibited 5-HT3A and a3b4 nACh receptor-mediated ion currents when present outside of the cell but not when injected intracellularly. We also examined the effect of these agents on oocytes expressing the gustatory cGMP-gated ion channel, which is known to have a cGMP binding site on the intracellular side of the plasma membrane and is only activated by cytosolic cGMP. Rg3 inhibited cGMP-gated ion currents when applied extracellularly or to an outside-out patch clamp, but not when injected into the cytosol or when using an excised inside-out patch clamp. These results indicate that Rg3 and M4 regulate ligand-gated ion channel activity from the extracellular side.
authors.affiliation: Research Laboratory for the Study of Ginseng Signal Transduction and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Jeong
authors.forename: Tal Su
authors.initials: TS
authors.lastname: Ha
authors.forename: Chul-Seung
authors.initials: CS
authors.lastname: Park
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Jin Su
authors.initials: JS
authors.lastname: Han
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.forename: Sung-Ryong
authors.initials: SR
authors.lastname: Ko
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D036145:Ginsenosides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D008024:Ligands; D015394:Molecular Structure; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D036145:Ginsenosides; D008024:Ligands; D011978:Receptors, Nicotinic; D044406:Receptors, Serotonin, 5-HT3; C403530:nicotinic receptor alpha3beta4; D006152:Cyclic GMP