Inhibitory effect of thiopental on ultra-rapid delayed rectifier K+ current in H9c2 cells.
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.
Suzuki
Hideki
H
Department of Pediatrics, Fukushima Medical University, School of Medicine, Fukushima 960-1295, Japan.
Momoi
Nobuo
N
Ono
Tomoyuki
T
Maeda
Sachiko
S
Shikama
Yayoi
Y
Matsuoka
Isao
I
Suzuki
Hitoshi
H
Kimura
Junko
J
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*
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