大电导钙激活钾通道在氯喹调节气管平滑肌张力中的作用

发布时间：2018-10-24 16:29

【摘要】：大电导钙依赖的钾通道(BK通道)是否参与氯喹舒张预收缩气管平滑肌的过程尚不清楚。在本研究中我们发现,iberiotoxin(IbTx,BK通道特异性阻断剂)和氯喹都能阻断小鼠气管平滑肌细胞中的自发性瞬时外向电流(Spontaneous transient outward currents,STOCs),这意味着氯喹可以阻断BK通道。我们又进一步发现了氯喹能阻断钙火花(Ca2+sparks)和咖啡因引起的细胞Qg钙升高,表明氯喹能阻断兰尼碱受体(Ryanodine receptors,RyRs)。此外,还发现了氯喹可以从气管平滑肌细胞内膜完全阻断BK通道的单通道电流,从细胞外膜也能部分阻断该电流。这些结果表明,氯喹通过阻断兰尼碱受体和BK通道抑制了自发性瞬时外向电流。另外,我们还发现乙酰胆碱(ACH)预刺激情况下低浓度氯喹(3.16μM,31.6μM)能引起气管环微小的收缩,增加氯喹浓度(100μM,316μM,1 mM)则能引起预收缩的气管环完全舒张。当在使用ACH刺激前加入BK通道特异性阻断剂Paxilline(Pax)或IbTx后,低浓度氯喹引起的小收缩消失,高浓度氯喹引起的舒张不受任何影响。我们的实验结果表明氯喹阻断BK通道和兰尼碱受体,使自发性瞬时外向电流受抑制,引起细胞收缩,而这一收缩可以被高浓度氯喹引起的舒张抵消,最终氯喹使预收缩的气管环舒张。
[Abstract]:It is not clear whether large calcium-dependent potassium channel (BK channel) is involved in chloroquine relaxation of tracheal smooth muscle. In this study, we found that both, iberiotoxin (IbTx,BK channel specific blockers) and chloroquine could block spontaneous transient outward current (Spontaneous transient outward currents,STOCs) in mouse tracheal smooth muscle cells, suggesting that chloroquine could block BK channels. We further found that chloroquine can block calcium elevation of Qg induced by calcium sparks (Ca2 sparks) and caffeine, suggesting that chloroquine can block Lanni base receptor (Ryanodine receptors,RyRs). In addition, chloroquine could completely block the single channel current of BK channel from the intima of tracheal smooth muscle cells and partly block the current from the extracellular membrane. These results suggest that chloroquine inhibits spontaneous transient outward currents by blocking Lannidine receptors and BK channels. In addition, we also found that low concentration chloroquine (3.16 渭 m) (31.6 渭 M) induced slight contraction of tracheal ring under prestimulation of acetylcholine (ACH), and that increased chloroquine concentration (100 渭 M ~ 316 渭 M ~ (-1 mM) could induce complete relaxation of the precontracted tracheal ring. When BK channel specific blockers Paxilline (Pax) or IbTx were added before ACH stimulation the small contraction induced by low concentration chloroquine disappeared and the relaxation induced by high concentration chloroquine was not affected. Our results show that chloroquine blocks BK channels and Lanni base receptors, inhibits spontaneous transient outward currents and causes cell contraction, which can be counteracted by high chloroquine induced relaxation. Eventually chloroquine relaxes the precontracted tracheal ring.
【学位授予单位】：中南民族大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R96

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