title: THE INHIBITORY EFFECT OF PACLITAXEL ON (Kv2.1) K+ CURRENT IN H9c2 CELLS.
abstract: Using the whole-cell voltage clamp technique, we investigated the effect of paclitaxel, an anticancer agent which promotes microtubule formation, on K(+) current in H9c2 cells originated from rat embryonic cardiac myocytes. Paclitaxel inhibited Kv2.1 voltage-dependent K(+) current (IKur) with ultra-rapidly activating and slowly inactivating kinetics in a concentration-dependent manner. The inhibitory effect of paclitaxel on IKur was time-dependent and more marked at 200 ms after the onset than at the beginning of the depolarizing pulse. The IC50 value of paclitaxel was 1.1 µM at 200 ms. The time-dependent inhibition suggests that paclitaxel might be an open channel blocker of Kv2.1. This inhibition of Kv2.1 may be involved in the adverse effects of paclitaxel on cardiac and neuronal cells.
authors.affiliation: Department of Pharmacology, Fukushima Medical University, School of Medicine.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kitamura
authors.forename: Kazuho
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ono
authors.forename: Junko
authors.initials: J
authors.lastname: Kimura
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats; D051669:Shab Potassium Channels / Q000037:antagonists & inhibitors*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020747:Calcium Channels, T-Type; C496991:Kcnb1 protein, rat; D051669:Shab Potassium Channels; D017239:Paclitaxel