尽管心力衰竭对窦房结细胞有心动过缓作用，但钙（Ca2+）循环特性仍得以保留。
Ca(2+) cycling properties are conserved despite bradycardic effects of heart failure in sinoatrial node cells.
作者信息
Verkerk Arie O, van Borren Marcel M G J, van Ginneken Antoni C G, Wilders Ronald
机构信息
Department of Anatomy, Embryology and Physiology, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
Department of Anatomy, Embryology and Physiology, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands ; Laboratory of Clinical Chemistry and Haematology, Rijnstate Hospital Arnhem, Netherlands.
出版信息
Front Physiol. 2015 Feb 2;6:18. doi: 10.3389/fphys.2015.00018. eCollection 2015.
BACKGROUND
In animal models of heart failure (HF), heart rate decreases due to an increase in intrinsic cycle length (CL) of the sinoatrial node (SAN). Pacemaker activity of SAN cells is complex and modulated by the membrane clock, i.e., the ensemble of voltage gated ion channels and electrogenic pumps and exchangers, and the Ca(2+) clock, i.e., the ensemble of intracellular Ca(2+) ([Ca(2+)]i) dependent processes. HF in SAN cells results in remodeling of the membrane clock, but few studies have examined its effects on [Ca(2+)]i homeostasis.
METHODS
SAN cells were isolated from control rabbits and rabbits with volume and pressure overload-induced HF. [Ca(2+)]i concentrations, and action potentials (APs) and Na(+)-Ca(2+) exchange current (INCX) were measured using indo-1 and patch-clamp methodology, respectively.
RESULTS
The frequency of spontaneous [Ca(2+)]i transients was significantly lower in HF SAN cells (3.0 ± 0.1 (n = 40) vs. 3.4 ± 0.1 Hz (n = 45); mean ± SEM), indicating that intrinsic CL was prolonged. HF slowed the [Ca(2+)]i transient decay, which could be explained by the slower frequency and reduced sarcoplasmic reticulum (SR) dependent rate of Ca(2+) uptake. Other [Ca(2+)]i transient parameters, SR Ca(2+) content, INCX density, and INCX-[Ca(2+)]i relationship were all unaffected by HF. Combined AP and [Ca(2+)]i recordings demonstrated that the slower [Ca(2+)]i transient decay in HF SAN cells may result in increased INCX during the diastolic depolarization, but that this effect is likely counteracted by the HF-induced increase in intracellular Na(+). β-adrenergic and muscarinic stimulation were not changed in HF SAN cells, except that late diastolic [Ca(2+)]i rise, a prominent feature of the Ca(2+) clock, is lower during β-adrenergic stimulation.
CONCLUSIONS
HF SAN cells have a slower [Ca(2+)]i transient decay with limited effects on pacemaker activity. Reduced late diastolic [Ca(2+)]i rise during β-adrenergic stimulation may contribute to an impaired increase in intrinsic frequency in HF SAN cells.
背景
在心力衰竭（HF）动物模型中，由于窦房结（SAN）的固有周期长度（CL）增加，心率降低。SAN细胞的起搏活动很复杂，受膜时钟（即电压门控离子通道、电生泵和交换体的集合）和钙（Ca2+）时钟（即细胞内Ca2+（[Ca2+]i）依赖性过程的集合）调节。SAN细胞中的HF导致膜时钟重塑，但很少有研究探讨其对[Ca2+]i稳态的影响。
方法
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。分别使用indo-1和膜片钳技术测量[Ca2+]i浓度、动作电位（APs）和钠钙交换电流（INCX）。
结果
HF SAN细胞中自发[Ca2+]i瞬变的频率显著降低（3.0±0.1（n = 40）对3.4±0.1 Hz（n = 45）；平均值±标准误），表明固有CL延长。HF减缓了[Ca2+]i瞬变衰减，这可以用较慢的频率和降低的肌浆网（SR）依赖性Ca2+摄取速率来解释。其他[Ca2+]i瞬变参数、SR Ca2+含量、INCX密度和INCX-[Ca2+]i关系均不受HF影响。联合AP和[Ca2+]i记录表明，HF SAN细胞中较慢的[Ca2+]i瞬变衰减可能导致舒张期去极化期间INCX增加，但这种效应可能被HF诱导的细胞内Na+增加所抵消。HF SAN细胞中的β-肾上腺素能和毒蕈碱刺激没有改变，除了在β-肾上腺素能刺激期间，Ca2+时钟的一个突出特征——舒张期末期[Ca2+]i升高较低。
结论
HF SAN细胞具有较慢的[Ca2+]i瞬变衰减，并对起搏活动影响有限。β-肾上腺素能刺激期间舒张期末期[Ca2+]i升高降低可能导致HF SAN细胞固有频率增加受损。
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