The widely used histamine receptor antagonists terfenadine and astemizole were shown to prolong the QT interval in electrocardiographic recordings in cases of overdose or inappropriate co-medications, indicating a possible interaction with cardiac K+ channels. Here, terfenadine and astemizole both inhibited the human ether-a-go-go related gene (HERG) encoded channels expressed in Xenopus oocytes at nanomolar concentrations in a use-and voltage-dependent fashion. In contrast, inhibition of other delayed rectifier (Kvl.1 and I& or inward rectifier K+ channels (IRKl) was much weaker and occurred only at high micromolar concentrations. These results suggest that blockade of HERG channels by terfenadine and astemizole might contribute to the cardiac side effects of these compounds.

The effect of verapamil and its enantiomers and metabolites on cardiac action potential repolarizing potassium channels was tested. For this purpose, the potassium channels Kv1.1, Kv1.5, Kir2.1, and HERG, and the IsK subunit of the IKs-channel complex were expressed in Xenopus oocytes and two-electrode voltage-clamp experiments were performed. Verapamil induced a concentration-dependent block of Kv1.1-, Kv1.5-, IKs-, and HERG-induced currents with IC₅₀ values of 14.0 ± 2.7 μM (n = 4), 5.1 ± 0.5 μM (n = 6), 161.0 ± 26.3 μM (n = 4), and 3.8 ± 0.2 μM (n = 5), respectively. The same potency of HERG channel inhibition was observed for the optical enantiomers (+)-verapamil (IC₅₀ = 3.5 ± 0.4 μM, n = 5) and (–)-verapamil (IC₅₀ = 4.0 ± 0.7 μM, n = 4), as well as the derivatives norverapamil (D591; IC₅₀ = 3.8 ± 0.3 μM, n = 4) and D703 (IC₅₀ = 2.2 ± 0.4 μM, n = 4). The verapamil metabolites D620 and D617 did not block HERG-induced currents at concentrations of up to 30 μM (n = 3). These results demonstrate that cardiac delayed rectifier potassium currents are sensitive targets to calcium channel blockers.

The addition of progesterone (1-100 mumol/l) to the extracellular fluid bathing rat hepatocytes led to a rapid and fully reversible depolarization of the cell membrane. The progesterone-induced depolarization was paralleled by a decrease of potassium selectivity and an increase of cell membrane resistance and was abolished in the presence of the potassium channel blocker barium. Accordingly, in whole cell recordings, progesterone led to a decrease of the cell membrane conductance. 17 alpha-Hydroxyprogesterone and beta-estradiol were less effective by a factor of 10, whereas cholesterol, corticosterone and hydrocortisone did not significantly alter the potential difference across the cell membrane. In conclusion, acute administration of progesterone depolarized rat hepatocytes by decreasing the potassium conductance of the cell membrane.

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