高血压病患者肠系膜动脉平滑肌细胞钙激活钾通道变化及前列腺素E_1对通道活性的影响

The changes in calcium-activated potassium channels of mesenteric artery smooth muscle in patient with essential hypertension and effects of prostaglandin E_1 on KCa channel

目的 探讨高血压病患者肠系膜动脉平滑肌细胞钙激活钾 (KCa)变化及前列腺素 (PG)E1 对通道活性的影响。方法 用酶消化法获取血管平滑肌细胞 ,以膜片钳技术检测KCa通道的活性 ,通过Pclamp专用软件实时采样记录其平均开放时间 (To) ,平均关闭时间 (Tc) ,平均开放概率 (Po)等。然后分别加入不同浓度的Ca2 +(10 - 8、10 - 7、10 - 6mol L)及PGE1 (10、2 0、40、10 0、2 0 0、40 0nmol L)后 ,再观察上述参数变化。结果 高血压病组肠系膜动脉平滑肌细胞KCa通道活性显著高于非高血压组 ,加入Ca2 +后 ,两组KCa通道均被明显激活 ,与加Ca2 +前比较 ,非高血压组Po增加了 18.4倍 ,而高血压病组Po仅增加了 1.7倍。PGE1 可使高血压病患者肠系膜动脉平滑肌细胞KCa通道To延长 ,Tc缩短 ,Po增加。结论 高血压病患者肠系膜动脉平滑肌细胞KCa通道活性明显高于非高血压者 ,但对Ca2 +的敏感性降低 ,PGE1 可明显激活高血压病患者肠系膜动脉平滑肌细胞KCa通道。

Objective To investigate the changes in Ca 2+ activated K + channels (KCa) of mesenteric artery smooth muscle cell(SMC) in patients with essential hypertension (EH) and the effects of prostaglandin (PG) E 1 on KCa channel.Methods Mesenteric artery branch from EH patients was digested by enzyme.Patch clamp technique was used to pull cell attached and inside out patches on mesenteric artery SMC from EH patients and the normotensive patients respectively.The signals of channel open probability (Po),open dwell time(To) and close dwell time(Tc),open channel number per patch were recorded.After adding Ca 2+ (10 -8 ～10 -6 mol/L)and PG E 1(10,20,40,100,200,400 nmol/L) to cytoplasm respectively,the above parameters were observed again.Results Compared with that of normotensive patients,the activities of KCa channels of patients with EH was higher.After adding Ca 2+ to cytoplasm,the Po of KCa channels in normotensive patients increased by 18.4 times,but it was enhanced only by 1.7 times in EH group.PG E 1 could affect KCa channel current and channel kinetics significantly in side out patches,causing increase in Po,protraction of To and curtailment of Tc of KCa channels in EH.Conclusions The activities of KCa channels of mesenteric artery SMC of patients with EH increased significantly,but the sensitivity to Ca 2+ decreased.The PG E 1 can activate KCa channels of mesenteric artery SMC of patients with EH.