Intracellular Ca2+ release contributes to automaticity in cat atrial pacemaker cells
Intracellular Ca2+ release contributes to automaticity in cat atrial pacemaker cells
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DOI：
10.1111/j.1469-7793.2000.00415.x
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发表时间：
2000-04-15
影响因子：
5.5
通讯作者：
Lipsius, SL
中科院分区：
文献类型：
--
作者：
Hüser, J;Blatter, LA;Lipsius, SL
1.调控心脏心房起搏器活动的细胞机制尚不清楚。在本研究中，我们使用穿孔膜片电压钳和共聚焦荧光显微镜来研究细胞内钙离子释放对猫右心房起搏细胞自律性的影响。在自发搏动的起搏细胞中，肌膜下细胞内钙离子浓度的升高伴随着舒张期最后1/3的去极化，这是由于肌浆网(SR)局部释放的钙离子引起的，即钙火花。低电压激活的T型钙电流(I-Ca，I-T)阻断剂镍(Ni2+；25-50mU/M)可降低舒张期去极化，延长起搏周期长度，抑制舒张期钙释放。电压钳分析表明，舒张期钙释放是电压依赖性的，并在-60 mV触发。Ni2+抑制低电压激活的钙释放。此外，低电压激活的Ca~(2+)释放与缓慢的内向电流平行，这可能是由于NaF-Ca~(2+)交换的刺激。窦房结和潜伏期心房起搏细胞均可见低电压激活的钙离子释放，而工作的心房肌细胞则无此现象。这些发现表明，低电压激活的I-Ca、I-T触发肌膜下钙火花，进而刺激Ina-Ca使起搏电位去极化到阈值。这一新的机制表明，I-Ca、I-T和肌膜下细胞内钙释放在正常的心房起搏器活动中起着关键作用，并可能参与异位房性心律失常的发生。
1. The cellular mechanisms governing cardiac atrial pacemaker activity are not clear. In the present study we used perforated patch voltage clamp and confocal fluorescence microscopy to study the contribution of intracellular Ca2+ release to automaticity of pacemaker cells isolated from cat right atrium.2. In spontaneously beating pacemaker cells, an increase in subsarcolemmal intracellular Ca2+ concentration occurred concomitantly with the last third of diastolic depolarization due to local release of Ca2+ from the sarcoplasmic reticulum (SR), i.e. Ca2+ sparks. Nickel (Ni2+; 25-50 mu M), a blocker of low voltage-activated T-type Ca2+ current (I-Ca,I-T), decreased diastolic depolarization, prolonged pacemaker cycle length and suppressed diastolic Ca2+ release.3. Voltage clamp analysis indicated that the diastolic Ca2+ release was voltage dependent and triggered at about -60 mV. Ni2+ suppressed low voltage-activated Ca2+ release. Moreover, low voltage-activated Ca2+ release was paralleled by a slow inward current presumably due to stimulation of Naf-Ca2+ exchange (INa-Ca). Low voltage-activated Ca2+ release was found in both sino-atrial node and latent atrial pacemaker cells but not in working atrial myocytes.4. These findings suggest that low voltage-activated I-Ca,I-T triggers subsarcolemmal Ca2+ sparks, which in turn stimulate INa-Ca to depolarize the pacemaker potential to threshold. This novel mechanism indicates a pivotal role for I-Ca,I-T and subsarcolemmal intracellular Ca2+ release in normal atrial pacemaker activity and may contribute to the development of ectopic atrial arrhythmias.