D型钠尿肽对豚鼠胃窦环形肌细胞钙敏感钾电流的影响及其作用机制

Effects of dendroaspis natriuretic peptide on calcium-activated potassium current and its mechanism in gastic antral circular smooth muscle of guinea-pig

关键词:  Ｄ型钠尿肽  钙敏感钾电流  钙依赖的钙释放  三磷酸肌醇受体  斯里兰卡肉桂咸受体

Key words:  dendroaspis natriuretic peptide  calcium - activated potassium channels  Ca2+ - induced Ca2+ release  inositol 1, 4, 5 - trisphosphate receptors  ryanodine receptor

摘要:

［目的］ 记录D型钠尿肽（DNP）对豚鼠胃窦环形肌钙敏感钾电流［IK(Ca)］的影响以探讨DNP抑制胃动力的离子通道机制。［方法］ 用全细胞式膜片钳技术观察DNP对豚鼠胃窦环形肌细胞IK(Ca) 和瞬间外向钾电流（STOCs）的影响。［结果］ DNP明显增加豚鼠胃窦环形肌IK(Ca) 和STOCs，并显示剂量依赖关系。0.1、1、10和100 nmol/L的DNP能增加IK(Ca) 的幅度，分别为（16.7±1.12）%、（26.5±2.3）%、（46.2±3.3）%和（58.3±3.7）%。细胞外液用无钙液或Rynodine受体的阻断剂均不能阻断此效应，但IP3受体的阻断剂肝素或鸟苷酸环化酶抑制剂LY83583能抑制这种效应。另外，cGMP敏感的磷酸酯酶抑制剂Zaparinast可明显增强DNP对STOCs的增加作用。［结论］ DNP通过增加cGMP的产生和激活IP3受体使豚鼠胃窦环形肌细胞上IK(Ca) 增加，细胞超极化，从而实现对胃窦环形肌的舒张作用。

Abstract:

［Objective］ To investigate the effect of dendroaspis natriuretic peptide (DNP) on calcium-activated potassium current. ［IK(Ca)］and its mechanism in gastric antral circular smooth muscle cells (SMCs). ［Methods］ IK(Ca) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique. ［Results］ DNP concentration-dependently increased macroscopic IK(Ca) and STOCs in freshly isolated gastric antral circular SMCs of guinea pig. The significant increase induced by DNP in the amplitude of IK(Ca) at 60 mV were (16.7±1.12)%, (26.5±2.3)%, (46.2±3.3)%, and (58.3±3.7)%, respectively, following applications of DNP at 0.1, 1, 10 and 100 nmol/L. The effects of DNP on IK(Ca) and/or STOCs were not blocked by calcium-free bath solution or the ryanodine receptor (RyR) antagonist ryanodine (10 μmol/L), but they were inhibited by the inositol triphosphate receptor (IP R) inhibitor heparin or the guanylate cyclase inhibitor LY83583.Moreover, DNP-induced increase in STOCs was potentiated by the cyclic guanosine monophosphate (cGMP) sensitive phosphoesterase inhibitor zaprinast. ［Conclusion］ Our results suggest that DNP increases IK(Ca) in gastric antral circular SMCs by increasing cGMP production and activating IP3 receptor.