目的 研究?；撬徭V配合物（TMCC）對獲得性長QT綜合征（LQTS）模型的抗心律失常作用及作用機(jī)制。方法 采用Langendorff逆行主動脈灌流酶解法，急性分離獲得豚鼠單個心室肌細(xì)胞；建立表達(dá)KCNQ1/KCNE1基因的HEK293細(xì)胞模型。色原烷醇293B （5 μmol/L）用來建立LQTS模型，采用全細(xì)胞膜片鉗技術(shù)記錄TMCC （0.01、0.10、1.00 mmol/L）對正常和LQTS模型豚鼠心室肌細(xì)胞動作電位和緩慢激活延遲整流外向鉀通道（I_Ks）電流的影響。結(jié)果 色原烷醇293B可以顯著延長50%和90%復(fù)極化動作電位持續(xù)時間（APD₅₀和APD₉₀），0.01、0.10、1.00 mmol/L TMCC可以顯著減弱色原烷醇293B延長APD₅₀和APD₉₀的作用（P<0.05、0.01）。TMCC （0.01、0.10、1.00 mmol/L）對抗色原烷醇293B對I_Ks電流的抑制作用，減弱色原烷醇293B對I-V曲線的下移，0.1、1.0 mmol/L濃度組顯著減弱色原烷醇293B對I_Ks電流的抑制作用（P<0.01），呈現(xiàn)對抗LQTS的作用。結(jié)論 TMCC通過縮短動作電位復(fù)極時程，增大被抑制的I_Ks電流，發(fā)揮一定的抗LQTS的作用。

objective The anti-arrhythmic effect of Taurine-Magnesium Coordination Compound (TMCC) was assessed on the model of long QT syndrome (LQTS). Methods Chromanol 293B (5 μmol/L) was used to establish the LQTS model in guinea pig ventricular myocytes and to inhibit HEK293 cells stably expressing I_Ks channels. All cells were incubated for 24 h in the absence and presence of drugs. The I_Ks current and action potentials were recorded by using the whole-cell patch-clamp technique. Results Chromanol 293B significantly prolonged APD₅₀ and APD₉₀ (P<0.01). TMCC could attenuate the effect of chromanol 293B on prolongation APD₅₀ and APD₉₀, which could be reversed significantly by TMCC (0.01, 0.1, 1.0 mmol/L) (P<0.05 and 0.01). TMCC (0.01, 0.1, and 1 mmol/L) were concentration-dependently against the effect of chromanol 293B on I_Ks current inhibition. The I_Ks I-V curve was shifted downwards by chromanol 293B (5 μmol/L), while upwards by TMCC. TMCC (0.01, 0.10, and 1.00 mmol/L) could restore the decrease of peak I_Ks due to chromanol 293B (P<0.01). Conclusion It was suggested that TMCC have antiarrhythmic effect on LQTS through shortening the action potential duration and increasing the inhibited I_Ks current.

R926

國家自然科學(xué)基金面上項(xiàng)目（81373410）