Inhibitory effects of SKF96365 on the activities of K+ channels in mouse small intestinal smooth muscle cells

In order to investigate the effects of SKF96365 (SKF), which is a non-selective cationic channel blocker, on K+ channel currents, we recorded currents through ATP sensitive K+ (I-KATB), voltage-gated K+ (I-Kv) and Ca2+ activated K+ channels (I-BK) in the absence and presence of SKF in single small intestinal myocytes of mice with patch-clamp techniques. SKF (10 mu M) reversibly abolished I-KATP that was induced by cromakalim (10 mu M), which is a selective ATP sensitive K+ channel opener. These inhibitory effects were induced in a concentration-dependent and voltage-independent manner. The 50% inhibitory concentration (IC50) was 0.85 mu M, which was obviously lower than that reported for the muscarinic cationic current. In addition, SKF (1 mu M approximate to the IC50 value in I-KATP suppression) reversibly inhibited the I-Kv that was induced by repetitive depolarizing pulses from -80 to 20 mV. However, the extent of the inhibitory effects was only similar to 30%. In contrast, SKF (1 mu M) had no significant effects on spontaneous transient I-BK and caffeine-induced I-BK. These results indicated that SKF inhibited ATP sensitive K+ channels and voltage-gated K+ channels, with the ATP sensitive K+ channels being more sensitive than the voltage-gated K+ channels. These inhibitory effects on K+ channels should be considered when SKF is used as a cationic channel blocker.