Ca(2+) cycling properties are conserved despite bradycardic effects of heart failure in sinoatrial node cells.
Ca(2+) cycling properties are conserved despite bradycardic effects of heart failure in sinoatrial node cells.
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DOI：
10.3389/fphys.2015.00018
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发表时间：
2015
影响因子：
4
通讯作者：
Wilders R
中科院分区：
文献类型：
--
作者：
Verkerk AO;van Borren MM;van Ginneken AC;Wilders R
背景资料：在心力衰竭（HF）的动物模型中，由于窦房结（SAN）固有周期长度（CL）的增加，心率下降。SAN细胞的起搏器活动是复杂的，并由膜时钟调节，即，电压门控离子通道和产电泵和交换器的集合，以及Ca 2+时钟，即，细胞内Ca 2+（[Ca 2 +]i）依赖性过程的整体。HF在SAN细胞中导致膜时钟的重塑，但很少有研究检查其对[Ca 2 +]i稳态的影响。方法：分离正常家兔和容量压力超负荷致HF家兔的SAN细胞。[Ca2用indo-1和膜片钳方法分别测定细胞内[Na +]i浓度、动作电位（AP）和Na+-Ca ~（2+）交换电流（INCX）。结果如下：HF SAN细胞中自发[Ca 2 +]i瞬变的频率显著较低（3.0 ± 0.1（n = 40）vs. 3.4 ± 0.1 Hz（n = 45）;平均值± SEM），表明内源性CL延长。HF减慢了[Ca 2 +]i的瞬时衰减，这可以通过减慢频率和降低肌浆网（SR）依赖的Ca 2+摄取速率来解释。其他[Ca 2 +]i瞬态参数、SR Ca 2+含量、INCX密度和INCX-[Ca 2 +]i关系均不受HF影响。结合AP和[Ca 2 +]i记录表明，HF SAN细胞中[Ca 2 +]i瞬时衰减较慢可能导致舒张期去极化期间INCX增加，但这种作用可能被HF诱导的细胞内Na+增加所抵消。β-肾上腺素能和毒蕈碱刺激在HF SAN细胞中没有改变，除了舒张晚期[Ca 2 +]i升高（Ca 2+时钟的一个显著特征）在β-肾上腺素能刺激期间降低。结论：HF SAN细胞具有较慢的[Ca 2 +]i瞬时衰减，对起搏活动的影响有限。β-肾上腺素能刺激时舒张晚期[Ca 2 +]i升高减少可能导致HF SAN细胞固有频率增加受损。
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 Ca2+ clock, i.e., the ensemble of intracellular Ca2+ ([Ca2+]i) dependent processes. HF in SAN cells results in remodeling of the membrane clock, but few studies have examined its effects on [Ca2+]i homeostasis. Methods: SAN cells were isolated from control rabbits and rabbits with volume and pressure overload-induced HF. [Ca2+]i concentrations, and action potentials (APs) and Na+–Ca2+ exchange current (INCX) were measured using indo-1 and patch-clamp methodology, respectively. Results: The frequency of spontaneous [Ca2+]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 [Ca2+]i transient decay, which could be explained by the slower frequency and reduced sarcoplasmic reticulum (SR) dependent rate of Ca2+ uptake. Other [Ca2+]i transient parameters, SR Ca2+ content, INCX density, and INCX-[Ca2+]i relationship were all unaffected by HF. Combined AP and [Ca2+]i recordings demonstrated that the slower [Ca2+]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 [Ca2+]i rise, a prominent feature of the Ca2+ clock, is lower during β-adrenergic stimulation. Conclusions: HF SAN cells have a slower [Ca2+]i transient decay with limited effects on pacemaker activity. Reduced late diastolic [Ca2+]i rise during β-adrenergic stimulation may contribute to an impaired increase in intrinsic frequency in HF SAN cells.
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影响因子：
37.8
作者：
Despa, S;Islam, MA;Bers, DM
通讯作者：
Bers, DM
影响因子：
20.1
作者：
Bogdanov, Konstantin Y.;Maltsev, Victor A.;Lakatta, Edward G.
通讯作者：
Lakatta, Edward G.
DOI：
10.1152/ajpheart.1996.270.5.h1726
发表时间：
1996-05-01
影响因子：
4.8
作者：
Arai, A;Kodama, I;Toyama, J
通讯作者：
Toyama, J
影响因子：
10.8
作者：
Díaz, ME;Graham, HK;Trafford, AW
通讯作者：
Trafford, AW
影响因子：
5.5
作者：
Briston, Sarah J.;Caldwell, Jessica L.;Trafford, Andrew W.
通讯作者：
Trafford, Andrew W.