Torilin from Torilis japonica (Houtt.) DC. blocks hKv1.5 channel current.
Torilin was purified from Torilis japonica (Houtt.) DC., and its effects on a rapidly activating delayed rectifier K+ channel (hKv1.5), cloned from human heart and stably expressed in Ltk- cells, as well as the corresponding K+ current (the ultrarapid delayed rectifier, I(KUR)) were assessed in human atrial myocytes. Using the whole cell configuration of the patch-clamp technique, torilin was found to inhibit the hKv1.5 current in time and voltage-dependent manners, with an IC50 value of 2.51+/-0.34 microM at +60 mV. Torilin accelerated the inactivation kinetics of the hKv1.5 channel, and slowed the deactivation kinetics of the hKv1.5 current, resulting in a tail crossover phenomenon. Additionally, torilin inhibited the hKv1.5 current in a use-dependent manner. These results strongly suggest that torilin is a type of open-channel blocker of the hKv1.5 channel.
Kwak
Yong Geun
YG
Department of Pharmacology, Chonbuk National University Medical School, Chonju, 561-756, Korea.
Kim
Dae Keun
DK
Ma
Tian-Ze
TZ
Park
Sun-Ah
SA
Park
Hoon
H
Jung
Young Hoon
YH
Yoo
Dong-Jin
DJ
Eun
Jae Soon
JS
D000818:Animals; D019661:Apiaceae / Q000737:chemistry*; D002460:Cell Line; D002850:Chromatography, Gel / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005638:Fruit / Q000737:chemistry; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D018408:Patch-Clamp Techniques / Q000379:methods; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D045789:Sesquiterpenes, Guaiane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D014162:Transfection
D051666:Kv1.5 Potassium Channel; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D045789:Sesquiterpenes, Guaiane; C112694:torilin