猪冠状动脉平滑肌细胞的自发瞬时外向电流的特性(英文)  

Characteristic of spontaneous transient outward potassium currents in vascular smooth muscle cells of porcine coronary artery

作　　者：蔡芳[1] 李鹏云[1] 杨艳[1] 刘智飞[1] 李妙龄[1] 周文[1] 裴杰[1] 程俊[1] 兰欢[1] Joachim B.Grammer 曾晓荣[1] 

机构地区：[1]泸州医学院心肌电生理学研究室,泸州646000 [2]德国慕尼黑心脏中心心血管外科研究所,慕尼黑80636

出　　处：《生理学报》2007年第1期27-34,共8页Acta Physiologica Sinica

基　　金：This work was supported by the National Natural Science Foundation of China (No. 30370527)

摘　　要：自发瞬时外向电流(spontaneous transient outward currents,STOCs)在小动脉的肌源性调节中起着非常重要的作用。本文应用穿孔膜片钳技术记录了猪冠状动脉平滑肌细胞上的STOCs,研究了其基本特性以及调节。结果显示:STOCs有明显的电压依赖性和钙依赖性,其频率和幅度具有变异性。STOCs可以随机叠加在阶跃刺激方案和斜坡刺激方案引出的全细胞钾电流上。STOCs可被大电导钙激活钾(large-conductance Ca2+-activated potassium,BKCa)通道的特异性阻断剂ChTX、螯合胞外钙离子和50μmol／L ryanodine完全抑制。钙离子载体A23187可以明显增加STOCs的幅度和频率;而L型钙通道阻断剂verapamil和CdCl2对STOCs的影响很小。咖啡因使STOCs瞬时爆发性增加,然后抑制。钠离子载体可明显增加STOCs的频率;钠钙交换体选择性抑制剂KB-R7943可明显抑制STOCs。由此可以认为STOCs是BKCa通道介导的。STOCs的产生和激活依赖于经钠钙交换的钙内流和经肌浆网ryanodine受体介导的钙释放,钠钙交换可能决定钙库重载,而细胞膜下肌浆网的胞内钙释放(钙火花)所致的局部钙浓度瞬时增加激活与其相邻的BKCa通道,产生STOCs。Spontaneous transient outward currents （STOCs） play an important role in the myogenic regulation of small artery tone, such as coronary artery. In the present study, we investigated the electrophysiological properties and the regulation of STOCs in vascular smooth muscle cells （VSMCs） of porcine coronary artery by perforated patch-clamp technique. Our data showed that STOes were dependent on voltage and extracellular calcium and they were highly variable in amplitudes and frequencies. STOCs superimposed stochastically onto whole-cell K^＋ currents induced by step and ramp protocols. STOCs were completely abolished by ChTX [inhibitor of large-conductance Ca^2＋-activated potassium （BKca） channels], removal of extracellular Ca^2＋, or addition of ryanodine （50 pmol/L） respectively. In contrast, CdCl2 and verapamil, inhibitors of voltage-dependent L-type Ca^2＋ channels, had little effect on STOes. Caffeine （5 mmol/L） transiently increased STOCs （hump）, followed by a temporary inhibition. Ca^2＋ ionophore A23187 increased both amplitude and frequency of STOCs. Na^2＋ ionophore monensin increased the frequency of STOCs. STOCs were strongly inhibited by KB-R7943, a selective inhibitor of the reverse mode of the Na^2＋/Ca^2＋ exchanger. Based on these observations, we conclude that STOCs are mediated by BKca channels. The generation and activation of STOCs depend upon Ca^2＋ influx through Na^2＋/Ca^2＋ exchange and release of Ca^2＋ from sarcoplasmic reticulum （SR） via ryanodine receptors. This suggests that Na＋/Ca^2＋ exchange determines calcium store refilling. Recycling of entering Ca^2＋ from superficial SR may locally elevate Ca^2＋ concentration at the plasma membrane, thereby activating BKca channels and then initiating STOCs.

关 键 词：膜片钳技术 平滑肌 钾通道 钠钙交换体 RYANODINE受体 

分 类 号：Q46[生物学—生理学]