title: Activation of lysophosphatidic acid receptor by gintonin inhibits Kv1.2 channel activity: involvement of tyrosine kinase and receptor protein tyrosine phosphatase α.
abstract: Gintonin is a novel ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand. The primary action of gintonin is to elicit a transient increase in [Ca(2+)]i via activation of LPA receptor subtypes. Voltage-gated potassium (Kv) channels play important roles in synaptic transmission in nervous systems. The previous reports have shown that Kv channels can be regulated by Gαq/11 protein-coupled receptor ligands. In the present study, we examined the effects of gintonin on Kv1.2 channel activity expressed in Xenopus oocytes after injection of RNA encoding the human Kv1.2 α subunit. Gintonin treatment inhibited Kv1.2 channel activity in reversible and concentration-dependent manners. The inhibitory effect of gintonin on Kv1.2 channel activity was blocked by active phospholipase C inhibitor, inositol 1,4,5-triphosphate receptor antagonist, and intracellular Ca(2+) chelator. The co-expression of active receptor protein tyrosine phosphatase α (RPTPα) with Kv1.2 channel greatly attenuated gintonin-mediated inhibition of Kv1.2 channel activity, but attenuation was not observed with catalytically inactive RPTPα. Furthermore, neither genistein, a tyrosine kinase inhibitor, nor site-directed mutation of a tyrosine residue (Y132 to Y132F), which is phosphorylated by tyrosine kinase of the N-terminal of the Kv1.2 channel α subunit, significantly attenuated gintonin-mediated inhibition of Kv1.2 channel activity. These results indicate that the gintonin-mediated Kv1.2 channel regulation involves the dual coordination of both tyrosine kinase and RPTPα coupled to this receptor. Finally, gintonin-mediated regulation of Kv1.2 channel activity might explain one of the modulations of gintonin-mediated neuronal activities in nervous systems.
authors.affiliation: Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, 143-701, Republic of Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Choi
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Hwang
authors.forename: Hyeon-Joong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jeehae
authors.initials: J
authors.lastname: Rhee
authors.forename: Chihye
authors.initials: C
authors.lastname: Chung
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
mesh_terms: D000818:Animals; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D051663:Kv1.2 Potassium Channel / Q000037:antagonists & inhibitors* / Q000502:physiology*; D009097:Multienzyme Complexes / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000819:agonists* / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D051663:Kv1.2 Potassium Channel; D009097:Multienzyme Complexes; D010936:Plant Extracts; D049368:Receptors, Lysophosphatidic Acid; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases
keywords: G-protein coupled receptor; GPCR; GT; Ginseng; Gintonin; LPA receptor; Potassium channel; RPTP alpha; Receptor protein tyrosine phosphatase α; Tyrosine kinase; gintonin; lysophosphatidic acid receptor; tyrosine phosphatase alpha