Key result
SKF96365 reversibly inhibited ATP-sensitive K+ channels in mouse small intestinal smooth muscle cells with an IC50 of 0.85 µM, demonstrating higher sensitivity than voltage-gated K+ channels.
SKF96365 inhibits ATP-sensitive and voltage-gated K+ channels in mouse small intestinal smooth muscle cells, which should be considered when using it as a cationic channel blocker.
Warrants caution interpreting SKF96365 effects in smooth muscle studies; leaves open its utility as a selective KATP probe pending in vivo validation.
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(+) (IKATP), voltage-gated K(+) (IKv) and Ca(2+) activated K(+) channels (IBK) in the absence and presence of SKF in single small intestinal myocytes of mice with patch-clamp techniques. SKF (10 µM) reversibly abolished IKATP that was induced by cromakalim (10 µM), 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 µM, which was obviously lower than that reported for the muscarinic cationic current. In addition, SKF (1 µM ≈ the IC50 value in IKATP suppression) reversibly inhibited the IKv that was induced by repetitive depolarizing pulses from -80 to 20 mV. However, the extent of the inhibitory effects was only ~30%. In contrast, SKF (1 µM) had no significant effects on spontaneous transient IBK and caffeine-induced IBK. 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.
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Tanahashi et al. (2015) studied None (in vitro mouse small intestinal smooth muscle cells). SKF96365 vs. Absence of SKF96365 was evaluated on Inhibition of ATP-sensitive K+ channels (IKATP) (IC50 0.85 µM). SKF96365 reversibly inhibited ATP-sensitive K+ channels in mouse small intestinal smooth muscle cells with an IC50 of 0.85 µM, demonstrating higher sensitivity than voltage-gated K+ channels.
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