Aaronson Philip Irving, Sarwar Uzma, Gin Stephanie, Rockenbauch Uli, Connolly Michelle, Tillet Alexandra, Watson Sarah, Liu Bing, Tribe Rachel Marie
Division of Asthma, Allergy and Lung Biology, King's College London, London.
Br J Pharmacol. 2006 Apr;147(7):815-24. doi: 10.1038/sj.bjp.0706644.
The roles of voltage-gated (K(V)) and large conductance Ca2+-activated K+ (BK(Ca)) channels in regulating basal contractility in myometrial smooth muscle are unresolved. The aim of this study was to determine the effects of inhibition of these channels on spontaneous rhythmic contraction in myometrial strips from four groups of rats: nonpregnant and during early (day 7), mid- (day 14), and late (day 21) pregnancy. BK(Ca) channels were inhibited using iberiotoxin (1-100 nM), paxilline (1-10 microM) or penitrem A (1-500, or 3000 nM); K(V) channels were inhibited using tetraethylammonium (TEA; 1-10 mM) and/or 4-aminopyridine (4-AP; 1-5 mM). Contractility was assessed as mean integral tension (MIT). Time/vehicle controls were also performed. None of the selective BK(Ca) channel inhibitors significantly affected contractility in myometrial strips from either nonpregnant or pregnant animals. 4-AP caused concentration-dependent increases in MIT in myometrium in all four groups. TEA (5 and 10 mM) significantly increased MIT in myometrium from nonpregnant, and mid- and late pregnant rats, but not in myometrium from early pregnant rats. TEA and 4-AP still caused an increase in MIT following treatment with 3000 nM penitrem A or a combination of propranolol, phentolamine, atropine (all 1 microM) and capsaicin (10 microM) in myometrial strips from nonpregnant rats. These results indicate that whereas BK(Ca) channels play little or no part in controlling basal rhythmicity in rat myometrium, K(V) channels appear to play a crucial role in this regard, especially during mid- and late pregnancy.
电压门控钾通道（K(V)）和大电导钙激活钾通道（BK(Ca)）在调节子宫肌层平滑肌基础收缩性中的作用尚未明确。本研究的目的是确定抑制这些通道对四组大鼠子宫肌条自发节律性收缩的影响：未孕大鼠以及妊娠早期（第7天）、中期（第14天）和晚期（第21天）的大鼠。使用iberiotoxin（1 - 100 nM）、paxilline（1 - 10 microM）或penitrem A（1 - 500或3000 nM）抑制BK(Ca)通道；使用四乙铵（TEA；1 - 10 mM）和/或4 - 氨基吡啶（4 - AP；1 - 5 mM）抑制K(V)通道。收缩性通过平均积分张力（MIT）进行评估。同时也进行了时间/溶剂对照实验。所有选择性BK(Ca)通道抑制剂均未对未孕或妊娠动物的子宫肌条收缩性产生显著影响。4 - AP使所有四组子宫肌层的MIT呈浓度依赖性增加。TEA（5和10 mM）显著增加了未孕、妊娠中期和晚期大鼠子宫肌层的MIT，但对妊娠早期大鼠子宫肌层无此作用。在用3000 nM penitrem A或普萘洛尔、酚妥拉明、阿托品（均为1 microM）和辣椒素（10 microM）联合处理未孕大鼠的子宫肌条后，TEA和4 - AP仍使MIT增加。这些结果表明，BK(Ca)通道在控制大鼠子宫肌层基础节律性方面作用很小或不起作用，而K(V)通道在这方面似乎起着关键作用，尤其是在妊娠中期和晚期。
