title: Inhibitory effect of thiopental on ultra-rapid delayed rectifier K+ current in H9c2 cells.
abstract: Using the whole-cell voltage clamp technique, we investigated the effects of thiopental on membrane currents in H9c2 cells, a cell line derived from embryonic rat heart. Thiopental blocked a rapidly activating, very slowly-inactivating ultra-rapid type I(Kur)-like outward K(+) current in a concentration-dependent manner. The half-maximal concentration (IC(50)) of thiopental was 97 microM with a Hill coefficient of 1.2. The thiopental-sensitive current was also blocked by high concentrations of nifedipine (IC(50) = 9.1 microM) and 100 microM chromanol 293B, a blocker of slowly activating delayed rectifier K+ current (I(Ks)), but was insensitive to E-4031, an inhibitor of rapidly activating delayed rectifier K(+) current (I(Kr)). TEA (tetraethylammonium) at 5 mM and 4-AP (4-aminopiridine) at 1 mM reduced the K(+) current to 30.8 +/- 12.2% and 20.5 +/- 6.5% of the control, respectively. Using RT-PCR, we detected mRNAs of Kv2.1, Kv3.4, Kv4.1, and Kv4.3 in H9c2 cells. Among those, Kv2.1 and Kv3.4 have I(Kur)-type kinetics and are therefore candidates for thiopental-sensitive K(+) channels in H9c2 cells. This is the first report showing that thiopental inhibits I(Kur). This effect of thiopental may be involved in its reported prolongation of cardiac action potentials.
authors.affiliation: Department of Pediatrics, Fukushima Medical University, School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Nobuo
authors.initials: N
authors.lastname: Momoi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ono
authors.forename: Sachiko
authors.initials: S
authors.lastname: Maeda
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Shikama
authors.forename: Isao
authors.initials: I
authors.lastname: Matsuoka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Junko
authors.initials: J
authors.lastname: Kimura
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D051669:Shab Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051670:Shaw Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D013874:Thiopental / Q000494:pharmacology*
chemical_list: D000777:Anesthetics; D002839:Chromans; D051668:Delayed Rectifier Potassium Channels; C492014:Kcnc4 protein, rat; D026902:Potassium Channel Blockers; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D051670:Shaw Potassium Channels; D013449:Sulfonamides; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane; D009543:Nifedipine; D013874:Thiopental; D011188:Potassium