School of Physiology and Pharmacology, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
Exp Physiol. 2012 Oct;97(10):1131-9. doi: 10.1113/expphysiol.2012.065110. Epub 2012 May 4.
Recent data indicate that Ca(2+) cycling in isolated atrioventricular node (AVN) cells contributes to setting spontaneous rate. The aim of the present study was to extend this observation to the intact AVN in situ, by evaluating the effects of inhibiting sarcoplasmic reticulum Ca(2+) uptake with cyclopiazonic acid (CPA) on intact AVN spontaneous activity and its response to isoprenaline. A model of the AVN-paced heart was produced to investigate intact AVN automaticity, by surgical ablation of the sino-atrial node (SAN) in the rabbit Langendorff-perfused heart. Electrograms were recorded from a site close to the AVN (triangle of Koch), an atrial site above the AVN, the left atrium and right ventricle, enabling AVN pacing of the preparation to be confirmed. Before SAN ablation, the heart rate was 166.8 ± 5.4 beats min(-1). Ablation of the SAN was clearly indicated by a sudden and significant decrease of heart rate to 108.6 ± 9.6 beats min(-1) (P < 0.01, n = 10). Isoprenaline (100 nm) increased AVN rate to 187.8 ± 12.0 beats min(-1) after 1 min of application (P < 0.01, n = 10). Cyclopiazonic acid (10 and 30 μm) decreased AVN rate to 81.6 ± 4.8 (n = 9) and 77.4 ± 6.0 beats min(-1) (n = 7), respectively [P < 0.05, 10 or 30 μm CPA versus control (n = 10)] and also reduced the AVN rate increase in response to isoprenaline from 78.8 ± 10.0 to 46.8 ± 6.8 and 26.7 ± 5.3%, respectively (P < 0.01). These inhibitory effects of CPA on the intact AVN rate and its response to isoprenaline indicate that Ca(2+) cycling is important to the intact AVN spontaneous activity and its acceleration during sympathetic stimulation.
最近的数据表明，在分离的房室结（AVN）细胞中，Ca（2+）循环有助于设定自发性心率。本研究的目的是通过评估用环匹阿尼酸（CPA）抑制肌浆网 Ca（2+）摄取对完整 AVN 自发性活动及其对异丙肾上腺素反应的影响，将这一观察结果扩展到原位完整 AVN。通过在兔 Langendorff 灌流心脏中外科消融窦房结（SAN），制作 AVN 起搏心脏模型，以研究完整 AVN 自动性。从靠近 AVN 的部位（ Koch 三角）、AVN 上方的心房部位、左心房和右心室记录电图，从而确认对该标本进行 AVN 起搏。SAN 消融前，心率为 166.8±5.4 次/分钟。SAN 消融后，心率明显突然下降至 108.6±9.6 次/分钟（P<0.01，n=10），这清楚地表明 SAN 消融。异丙肾上腺素（100nm）在应用 1 分钟后将 AVN 率增加至 187.8±12.0 次/分钟（P<0.01，n=10）。环匹阿尼酸（10 和 30μm）将 AVN 率分别降低至 81.6±4.8（n=9）和 77.4±6.0 次/分钟（n=7）[P<0.05，10 或 30μmCPA 与对照（n=10）]，并分别将异丙肾上腺素引起的 AVN 率增加从 78.8±10.0 降低至 46.8±6.8 和 26.7±5.3%（P<0.01）。CPA 对完整 AVN 率及其对异丙肾上腺素反应的这种抑制作用表明，Ca（2+）循环对完整 AVN 自发性活动及其在交感刺激期间的加速很重要。
