title: The inhibitory effect of shakuyakukanzoto on K+ current in H9c2 cells.
abstract: Shakuyakukanzoto (shao-yao-gan-cao-tang) is a commonly used Chinese traditional herbal medicine for the treatment of acute pain with muscle cramp. However, its mechanism of action is unclear. We previously reported that a low concentration of Kanzo (licorice) and isoliquiritigenin, a component of licorice, inhibited the potassium (K(+)) current in H9c2 cells. Therefore, in the present study, we examined the effects of Shakuyakukanzoto, Shakuyaku or Kanzo on the K(+) current (IKur) in H9c2 cells. Shakuyakukanzoto inhibited IKur in a concentration-dependent manner. The half-maximal concentration of Shakuyakukanzoto was approximately 1.3 mg/mL and the Hill coefficient was 1.2. The order of potency of inhibiting IKur was Kanzo>Shakuyakukanzoto>Shakuyaku. Glycyrrhizin, a major component of licorice, had no inhibitory effect on IKur. A small interfering RNA experiment indicated that IKur was most likely to be Kv2.1 in H9c2 cells. Our results suggest that Shakuyakukanzoto may normalize intracellular and extracellular K(+) balance by inhibiting IKur and reducing K(+) efflux, while the Na(+)-K(+) pump promotes K(+) influx into myofibers. Consequently, excess K(+) may be reduced from external space of myofibers. This may be a part of the Shakuyakukanzoto mechanism for improving muscle pain.
authors.affiliation: Department of Anesthesiology, Fukushima Medical University.
authors.forename: Azusa
authors.initials: A
authors.lastname: Suganami
authors.forename: Kazuho
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ono
authors.forename: Hirotake
authors.initials: H
authors.lastname: Watanabe
authors.forename: Nahoko
authors.initials: N
authors.lastname: Hijioka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Murakawa
authors.forename: Junko
authors.initials: J
authors.lastname: Kimura
mesh_terms: D000818:Animals; D002460:Cell Line; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D009120:Muscle Cramp / Q000188:drug therapy / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D029596:Paeonia; D011188:Potassium / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D051669:Shab Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; C496991:Kcnb1 protein, rat; D034741:RNA, Small Interfering; D051669:Shab Potassium Channels; C038462:shakuyaku-kanzoh-toh; D019695:Glycyrrhizic Acid; D011188:Potassium