马来酸曲美布汀对结肠平滑肌细胞钙激活钾通道的影响

摘要

目的 研究马来酸曲美布汀对豚鼠结肠平滑肌细胞膜钙激活钾通道的影响.方法 酶解法急性分离单个豚鼠结肠平滑肌细胞,利用膜片钳技术在全细胞模式下记录钙激活钾电流[IK(ca)],用含有IK(ca)特异激动剂NS1619的生理盐水灌流细胞,使结肠平滑肌细胞处于超极化状态,检测给马来酸曲美布汀浓度分别为1.19 μmol/L、5.95 μmol/L、11.91 μmol/L后的结肠平滑肌细胞膜IK(ca).结果 浓度为1.19 μmoL/L、5.95 μmol/L、11.91 μmol/L的马来酸曲美布汀可抑制豚鼠单个结肠平滑肌细胞膜IK(ca)(P均＜0.01),当阶跃刺激为+80 mv时,其分别为超极化状态组的(65.87±4.80)％、(48.02±2.39)％、(18.88±2.29)％(P均＜0.01).结论 马来酸曲美布汀能抑制豚鼠结肠平滑肌细胞钙激活钾通道的开放,使细胞兴奋性升高,且呈浓度依赖性,这可能是马来酸曲美布汀治疗肠易激综合征便秘症状的机制之一.%Objective To study the effect of trimebutine on the calcium activated potassium channel of colonic smooth muscle cells (SMCs). Methods Smooth muscle cells were isolated freshly from the colon strips of guinea pig by enzymolysis, the calcium activated potassium currents [IK(ca) ] were recorded by patch clamp technique at whole cell model. The SMCs were perfused with physiologicalsaline (PSS) which contained NS1619-the calcium activated potassium channel's selective activator, causing the SMCs to be at the state of hyperpolarized. IK(ca) was detected when trimebutine at different concentrations (1. 19, 5.95, 11.91 (xmol/L). Results Trimebutine at three concentrations (1.19, 5.95, 11.91 nmol/L) could inhibit the IK(ca) of single colonic SMCs (all P <0.01). When stepped electrical stimulation parameter was 80 mv, IK(ca) were (65. 87 ±4. 80) %, (48. 02 ±2. 39)% and ( 18. 88 ±2. 29)% compared with hyperpolarized state group (P<0.01). Conclusion The results suggest that trimebutine can block the calcium activated potassium channel concentration-dependently and increase colonic SMCs' excitability. This may be one of the mechanisms of trimebutine in treatment of constipation symptom of IBS.