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(+) (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.
Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-Ku, Kyoto 603-8555, Japan.
Yasuyuki
Y
Tanahashi
Ban
B
Wang
Yuri
Y
Murakami
Toshihiro
T
Unno
Hayato
H
Matsuyama
Hiroshi
H
Nagano
Seiichi
S
Komori
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000378:metabolism
D002121:Calcium Channel Blockers; D007093:Imidazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D050052:TRPC Cation Channels; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole