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 μM with a Hill coefficient of 1.2. The thiopental-sensitive current was also blocked by high concentrations of nifedipine (IC
50 = 9.1 μM) and 100 μM 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.
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