Ginsenosides regulate ligand-gated ion channels from the outside.
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.
Lee
Byung-Hwan
BH
Research Laboratory for the Study of Ginseng Signal Transduction and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.
Jeong
Sang Min
SM
Ha
Tal Su
TS
Park
Chul-Seung
CS
Lee
Jun-Ho
JH
Kim
Jong-Hoon
JH
Kim
Dong-Hyun
DH
Han
Jin Su
JS
Kim
Hyoung-Chun
HC
Ko
Sung-Ryong
SR
Nah
Seung-Yeol
SY
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
D036145:Ginsenosides; D008024:Ligands; D011978:Receptors, Nicotinic; D044406:Receptors, Serotonin, 5-HT3; C403530:nicotinic receptor alpha3beta4; D006152:Cyclic GMP