Transmural heterogeneity of calcium activity and mechanical function in the canine left ventricle
Transmural heterogeneity of calcium activity and mechanical function in the canine left ventricle
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DOI：
10.1152/ajpheart.00748.2003
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发表时间：
2004-04-01
影响因子：
4.8
通讯作者：
Antzelevitch, C
中科院分区：
文献类型：
--
作者：
Cordeiro, JM;Greene, L;Antzelevitch, C
虽然心室肌内的电异质性一直是众多研究的焦点，很少有人注意到机械相关性。本研究探讨卸载细胞缩短，钙瞬变，和内向L型钙电流（I-Ca，I-L）的特点，心外膜，内膜，和中层心肌细胞分离犬左心室。使用视频边缘检测器记录未加载的细胞缩短，在加载有15 μ M fluo-3 AM的细胞中测量Ca 2+瞬变，并使用膜片钳技术获得电压和电流钳记录。收缩的峰值时间和潜伏期在心外膜细胞中最短，在内膜细胞中最长;中层心肌细胞显示中间的峰值时间。当使用均匀的电压钳方波引起收缩时，心外膜与内膜的区别持续存在，中层心肌细胞显示出与心外膜相当的峰值时间。当使用方波脉冲定量时，I-Ca、I-L的电流-电压关系和荧光-电压关系在三种细胞类型中相似。然而，峰值I-Ca，I-L和总电荷显着更大时，心外膜与内膜的动作电位波形被用来引发电压钳条件下的电流。肌浆网Ca 2+含量，评估快速应用咖啡因，是最大的心外膜细胞，并有助于更快的时间达到峰值。我们的数据点之间的三种心室细胞类型的钙稳态和机械功能的重要差异。这些差异用于同步心室壁的收缩。虽然这些区别部分是由三种细胞类型的电特性差异所赋予的，但兴奋-收缩偶联的内在差异是明显的。
Although electrical heterogeneity within the ventricular myocardium has been the focus of numerous studies, little attention has been directed to the mechanical correlates. This study examines unloaded cell shortening, Ca2+ transients, and inward L-type Ca2+ current (I-Ca,I-L) characteristics of epicardial, endocardial, and midmyocardial cells isolated from the canine left ventricle. Unloaded cell shortening was recorded using a video edge detector, Ca2+ transients were measured in cells loaded with 15 muM fluo-3 AM and voltage and current-clamp recordings were obtained using patch-clamp techniques. Time to peak and latency to onset of contraction were shortest in epicardial and longest in endocardial cells; midmyocardial cells displayed an intermediate time to peak. When contraction was elicited using uniform voltage-clamp square waves, epicardial versus endocardial distinctions persisted and midmyocardial cells displayed a time to peak comparable to that of epicardium. The current-voltage relationship for I-Ca,I-L and fluorescence-voltage relationship were similar in the three cell types when quantitated using square pulses. However, peak I-Ca,I- L and total charge were significantly larger when an epicardial versus endocardial action potential waveform was used to elicit the current under voltage-clamp conditions. Sarcoplasmic reticulum Ca2+ content, assessed by rapid application of caffeine, was largest in epicardial cells and contributed to a faster time to peak. Our data point to important differences in calcium homeostasis and mechanical function among the three ventricular cell types. These differences serve to synchronize contraction across the ventricular wall. Although these distinctions are conferred in part by differences in electrical characteristics of the three cell types, intrinsic differences in excitation-contraction coupling are evident.