Characterization of the hyperpolarization-activated current, I-f, in ventricular myocytes from human failing heart
Characterization of the hyperpolarization-activated current, I-f, in ventricular myocytes from human failing heart
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DOI：
10.1161/01.cir.95.3.568
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发表时间：
1997-02-04
期刊：
影响因子：
37.8
通讯作者：
Mugelli, A
中科院分区：
文献类型：
--
作者：
Cerbai, E;Pino, R;Mugelli, A
背景与疾病相关的电生理改变可能导致肥厚或衰竭心肌心律失常的易感性增加。在大鼠左心室肌细胞（LVMs）中表达I-f样电流，其幅度与心肌肥厚的严重程度呈线性相关。在这里，我们报告的发生和电生理特性的I-F在人类LVMs.Methods和结果LVMs分离心脏的三名男性患者进行心脏移植终末期心力衰竭由于缺血性扩张型心肌病。膜片钳技术用于记录I-f，即由超极化引起的钡不敏感、铯敏感、时间依赖性增加的内向电流。膜电容为244+/-27 pF（n=25）。在所有测试的细胞中均出现I-f;在-120 mV下测得的密度为2.1+/-0.3 pA/pF。用Boltzmann函数拟合I-f（n=24）的激活曲线;阈值为-55 mV;中点为-70.9+/-2.1 mV;斜率为-5.4+/-0.3 mV;最大电导率为19.6 ± 2.5pS/pF，细胞外铯对I-f的阻断具有电压依赖性。将细胞外钾离子浓度从25 mmol/L降至5.4 mmol/L时，逆转电位从-12.7+/-0.5降至-24.8+/-2.1 mV，电流电导下降64%。其电生理特征类似于先前在肥大大鼠LVMs中描述的那些，并表明I-f可能是严重心力衰竭患者的致心律失常机制。
Background Disease-associated electrophysiological alterations may contribute to the increased predisposition to arrhythmias of the hypertrophied or failing myocardium. An I-f-like current is expressed in rat left ventricular myocytes (LVMs), its amplitude being linearly related to the severity of cardiac hypertrophy. Here, we report the occurrence and electrophysiological properties of I-f in human LVMs.Methods and Results LVMs were isolated from hearts of three male patients undergoing cardiac transplantation for terminal heart failure due to ischemic dilated cardiomyopathy. The patch-clamp technique was used to record I-f, ie, a barium-insensitive, cesium-sensitive, time-dependent increasing inward current elicited on hyperpolarization. Membrane capacitance was 244+/-27 pF (n=25). I-f occurred in all cells tested; its density measured at -120 mV was 2.1+/-0.3 pA/pF. Activation curves of I-f (n=24) were fitted by a Boltzmann function; the threshold was -55 mV; midpoint, -70.9+/-2.1 mV; slope, -5.4+/-0.3 mV; and maximal specific conductance, 19.6+/-2.5 pS/pF. I-f blockade by extracellular cesium was voltage dependent. Reducing extracellular potassium concentration from 25 to 5.4 mmol/L caused a shift of the reversal potential from -12.7+/-0.5 to -24.8+/-2.1 mV and a 64% decrease of current conductance.Conclusions I-f is present in human LVMs. Its electrophysiological characteristics resemble those previously described in hypertrophied rat LVMs and suggest that I-f could be an arrhythmogenic mechanism in patients with severe heart failure.