Inhibitory effects of diazepam and midazolam on Ca2+ and K+ channels in canine tracheal smooth muscle cells

被引:28
|
作者
Yamakage, M [1 ]
Matsuzaki, T [1 ]
Tsujiguchi, N [1 ]
Honma, Y [1 ]
Namiki, A [1 ]
机构
[1] Sapporo Med Univ, Sch Med, Dept Anesthesiol, Chuo Ku, Sapporo, Hokkaido 0608543, Japan
关键词
Ca2+-activated; K+ channel; flumazenil; PK11195; voltage-dependent delayed rectifier K+ channel;
D O I
10.1097/00000542-199901000-00026
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Background: Benzodiazepines have a direct bronchodilator action in airway smooth muscle, but the mechanisms by which these agents produce muscle relaxation are not fully understood, The current study was performed to identify the effects of the benzodiazepines diazepam and midazolam on Ca2+ and K+ channels in canine tracheal smooth muscle cells. Methods: Whole-cell patch-clamp recording techniques were used to evaluate the effects of the benzodiazepines diazepam (10(-8) to 10(-3) M) and midazolam (10(-8) to 10(-3) M) on inward Ca2+ and outward K+ channel currents in dispersed canine tracheal smooth muscle cells. The effects of the antagonists flumazenil (10(-5) M) and PK11195 (10(-5) M) on these channels were also studied. Results: Each benzodiazepine tested significantly inhibited Ca2+ currents in a dose-dependent manner, with 10(-6) nr diazepam and 10(-5) ar midazolam each causing approximately 50% depression of peak voltage-dependent Ca2+ currents. Both benzodiazepines promoted the Inactivated state of the channel at more-negative potentials. The Ca2+-activated and voltage-dependent K+ currents were inhibited by diazepam and midazolam (> 10(-5) M and > 10(-4) M, respectively). Flumazenil and PK11195 had no effect on these channel currents or on the inhibitory effects of the benzodiazepines. Conclusions: Diazepam and midazolam had inhibitory effects on voltage-dependent Ca2+ channels, which lead to muscle relaxation. However, high concentrations of these agents were necessary to inhibit the K+ channels. The lack of antagonized effects of their antagonists is related to the non-gamma-aminobutyric acid-mediated electrophysiologic effects of benzodiazepines on airway smooth muscle contractility.
引用
收藏
页码:197 / 207
页数:11
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