Verkerk Arie O, Wilders Ronald, Coronel Ruben, Ravesloot Jan H, Verheijck E Etienne
Department of Physiology, Academic Medical Center, University of Amsterdam, The Netherlands.
Circulation. 2003 Aug 12;108(6):760-6. doi: 10.1161/01.CIR.0000083719.51661.B9. Epub 2003 Jul 28.
In animal models of heart failure (HF), heart rate decreases as the result of an increase in intrinsic cycle length of the sinoatrial node (SAN). In this study, we evaluate the HF-induced remodeling of membrane potentials and currents in SAN cells.
SAN cells were isolated from control rabbits and rabbits with volume and pressure overload-induced HF and patch-clamped to measure their electrophysiological properties. HF cells were not hypertrophied (capacitance, mean+/-SEM, 52+/-3 versus 50+/-4 pF in control). HF increased intrinsic cycle length by 15% and decreased diastolic depolarization rate by 30%, whereas other action potential parameters were unaltered. In HF, the hyperpolarization-activated "pacemaker" current (If) and slow component of the delayed rectifier current (IKs) were reduced by 40% and 20%, respectively, without changes in voltage dependence or kinetics. T-type and L-type calcium current, rapid and ultrarapid delayed rectifier current, transient outward currents, and sodium-calcium exchange current were unaltered.
In single SAN cells of rabbits with HF, intrinsic cycle length is increased as the result of a decreased diastolic depolarization rate rather than a change in action potential duration. HF reduced both If and IKs density. Since IKs plays a limited role in pacemaker activity, the HF-induced decrease in heart rate is attributable to remodeling of If.
在心力衰竭（HF）动物模型中，心率因窦房结（SAN）固有周期长度增加而降低。在本研究中，我们评估了HF诱导的SAN细胞动作电位和电流重塑。
从对照兔和容量及压力超负荷诱导的HF兔中分离出SAN细胞，采用膜片钳技术测量其电生理特性。HF细胞未发生肥大（电容，平均值±标准误，对照组为52±3 pF，HF组为50±4 pF）。HF使固有周期长度增加15%，舒张期去极化速率降低30%，而其他动作电位参数未改变。在HF状态下，超极化激活的“起搏”电流（If）和延迟整流电流的慢成分（IKs）分别降低了40%和20%，电压依赖性或动力学无变化。T型和L型钙电流、快速和超快延迟整流电流、瞬时外向电流以及钠钙交换电流均未改变。
在HF兔的单个SAN细胞中，固有周期长度增加是舒张期去极化速率降低的结果，而非动作电位时程改变所致。HF降低了If和IKs密度。由于IKs在起搏活动中作用有限，HF诱导的心率降低归因于If的重塑。
