塞来昔布对心脏钠离子通道Na_v1.5电生理特性的影响

Effect of Celecoxib on Electrophysiological Property of Cardiac Sodium Channel Na_v1.5

针对塞来昔布对与心脏毒性密切相关的钠离子通道Na_v1. 5电生理特性的影响进行了研究.采用全细胞膜片钳技术,检测塞来昔布对Na_v1. 5的电生理特性的影响,包括电流峰值、电压依赖性激活、电压依赖性失活以及恢复动力学.研究结果表明,塞来昔布对Na_v1. 5的峰电流具有抑制作用,且呈浓度依赖性,其抑制作用的IC50值为1. 54×10-8mol/L;塞来昔布促进了Na_v1. 5的激活及失活过程,使其难以恢复到静息状态.塞来昔布对Na_v1. 5峰电流的明显抑制作用,表明其潜在的心脏风险可能与Na_v1. 5密切相关.

The effect of celecoxib on electrophysiological property of Na v1.5 was studied,which was associated with cardiac toxicity.The effects of celecoxib on the electrophysiological properties of Nav1.5,including peak current,voltage-dependent activation,voltage-dependent inactivation and recovery kinetics,were investigated by whole cell patch clamp technique.The results showed that celecoxib inhibited the peak currents of Nav1.5 in a concentration-dependent manner with a calculated IC50 value of 1.54×10^-8 mol/L.Moreover,celecoxib promoted the activation and inactivation phase of Nav1.5,making it somewhat difficult to recover from the inactivation to the resting state.The prominent inhibition of celecoxib on Nav1.5 indicated that there might be a close relationship between potential cardiovascular risks and Nav1.5.