Background: Studies using isolated sinoatrial node (SAN) cells indicate that rhythmic spontaneous sarcoplasmic reticulum calcium release (Ca clock) plays an important role in SAN automaticity. In the intact SAN, cross-contamination of optical signals from the SAN and the right atrium (RA) prevent the definitive testing of Ca clock hypothesis. The aim of this study was to use a novel approach to selectively mapping the intact SAN to examine the Ca clock mechanism. Methods and Results: We simultaneously mapped intracellular Ca (Cai) and membrane potential (Vm) in 10 isolated, Langendorff-perfused normal canine RAs. The excitability of the RA was suppressed with high-potassium Tyrode's solution, allowing selective optical mapping of Vm and Cai of the SAN. Isoproterenol (ISO, 0.03μmol/L) decreased the cycle length of the sinus beats, and shifted the leading pacemaker site from the middle or inferior SAN to the superior SAN in all RAs. The Cai upstroke preceded the Vm in the leading pacemaker site by up to 18±2ms. ISO-induced changes to SAN were inhibited by ryanodine (3μmol/L), but not ZD7288 (3μmol/L), a selective If blocker. Conclusions: We conclude that, in the isolated canine RA, a high extracellular potassium concentration can suppress atrial excitability thus leading to SAN-RA conduction block, allowing selective optical mapping of the intact SAN. Acceleration of Ca cycling in the superior SAN underlies the mechanism of sinus tachycardia during sympathetic stimulation. ( Circ J 2012; 76: 309-316)
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机译：背景：使用隔离的窦房结（SAN）细胞进行的研究表明，有节奏的自发性肌浆网钙释放（Ca Clock）在SAN自动化中起着重要作用。在完整的SAN中，来自SAN和右心房（RA）的光信号交叉污染会阻止对Ca时钟假设的确定性测试。这项研究的目的是使用一种新颖的方法来选择性地映射完整的SAN，以检查Ca时钟机制。方法和结果：我们同时绘制了10个隔离的Langendorff灌注正常犬RA中的细胞内Ca（ca i ）和膜电位（V m ）的图。 RA的兴奋性被高钾Tyrode溶液抑制，从而可以选择性地映射SAN的V m 和Ca i 。异丙肾上腺素（ISO，0.03μmol/ L）缩短了窦性搏动的周期长度，并使所有起搏器中起搏器的主要部位从中级或下级SAN转移到了上级SAN。在起搏器领先部位，Ca i 上风先于V m 达18±2ms。 ISO诱导的SAN改变受到雷诺碱（3μmol/ L）的抑制，但不受ZD7288（3μmol/ L）的选择性I f 阻滞剂抑制。结论：我们得出的结论是，在孤立的犬类RA中，高细胞外钾浓度可以抑制心房兴奋性，从而导致SAN-RA传导阻滞，从而可以对完整SAN进行选择性光学定位。上级SAN中Ca循环的加速是交感神经刺激期间窦性心动过速的机制的基础。 （Circ J 2012; 76：309-316）
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