【摘要】 目的:研究心脏瞬间外向钾电流(I_to)在烧伤时的改变,探讨其在烧伤所致的心功能障碍中的作用。方法:将人类I_to通道的主要α亚基Kv4·3的cDNA转染到培养的CHO-K1细胞系,用膜片钳全细胞记录方式记录表达的通道电流,观察烧伤大鼠血清刺激对Kv4·3电流密度及门控动力学的影响。结果:体外表达的Kv4·3具有快速激活和快速失活的特性,与心肌细胞I_to电流相似。2%烧伤大鼠血清降低通道电流密度,+40mV电压刺激下,对照组电流密度为（67·6±15·1）pA/pF,烧伤血清处理组为（32·3±9·7）pA/pF,P<0·05。电压依赖性Kv4·3失活发生负向移位,对照组半数最大失活膜电位（V0·5）为（-41·1±7·0）mV,而烧伤血清处理组为（-76·2±9·8）mV,P<0·05。烧伤血清使Kv4·3从失活中恢复的幅度和速率也有所降低。结论:严重烧伤时机体产生并释放抑制I_to功能物质入血,通过循环作用于心肌细胞I_to通道,引起APD延长,QT间期离散。更多还原

【Abstract】 AIM: To study I_ to channel function in severe burn and its contribution to cardiac dysfunction induced by severe burn. METHODS: CHO-K1 cells were transfected with human Kv4.3, the major subunit of human I_ to channel. The expressed Kv4.3 channels were recorded by whole-cell patch clamp and the effects of rat burn serum on Kv4.3 current densities and kinetics were observed. RESULTS: Kv4.3 channels expressed in CHO-K1 cells were endowed with the characterization of fast activation and inactivation, which was quite similar to that of native I_ to channels in cardiomyocytes. Rat’s burn serum at the concentration of 2% decreased the current density significantly. At +40 mV, the current density in control group was (67.6±15.1) pA/pF, in contrast to (32.3±9.7)pA/pF in burn serum-treated group (P<0.05). The voltage dependent Kv4.3 inactivation was negatively shifted by burn serum. V_ 0.5 of inactivation was shifted from ( -41.1 ±7.0) mV in control group to ( -76.2 ±9.8) mV in burn serum treated group. Burn serum also had a mild impairment effect on Kv4.3 channel’s recovery from inactivation by decreasing percentage and rate of recovery. CONCLUSIONS: In severe burns, substances that have the effects of suppressing I_ to function are produced and release to the blood, then are carried to cardiomyocytes by circulation, and down-regulate I_ to in situ. This process results in action potential duration (APD) prolongation and QT dispersion observed in burn. With the prolongation of APD, the heart has a high risk to arrhythmia and Ca~ 2+ overload in cardiomyocytes, which might partially contribute to the pathogenesis of cardiac dysfunction in severe burn.更多还原