塞来昔布对心脏钠离子通道Na_v1.5电生理特性的影响
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摘要
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 Na_v1. 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 Na_v1. 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 Na_v1. 5,making it somewhat difficult to recover from the inactivation to the resting state. The prominent inhibition of celecoxib on Na_v1. 5 indicated that there might be a close relationship between potential cardiovascular risks and Na_v1. 5.
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 Na_v1. 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 Na_v1. 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 Na_v1. 5,making it somewhat difficult to recover from the inactivation to the resting state. The prominent inhibition of celecoxib on Na_v1. 5 indicated that there might be a close relationship between potential cardiovascular risks and Na_v1. 5.
引文
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