Spatial non-uniformity of excitation-contraction coupling can enhance arrhythmogenic-delayed afterdepolarizations in rat cardiac muscle
Spatial non-uniformity of excitation-contraction coupling can enhance arrhythmogenic-delayed afterdepolarizations in rat cardiac muscle
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DOI：
10.1093/cvr/cvn162
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发表时间：
2008-10-01
影响因子：
10.8
通讯作者：
Shimokawa, Hiroaki
中科院分区：
文献类型：
--
作者：
Miura, Masahito;Wakayama, Yuji;Shimokawa, Hiroaki
目的：我们研究了非均匀肌肉收缩是否通过在收缩区和拉伸区之间的边界区（BZ）内从肌丝中分离Ca（2+）来影响延迟后去极化（DADs）。方法和结果测定了31只大鼠心室小梁的力、肌节长度（SL）、膜电位和[Ca(2+)](i)动力学。将肌肉的有限区域暴露于含有20 mmol/L 2,3-丁二酮一肟（BDM）的溶液射流中，产生不均匀的肌肉收缩。在24℃，[Ca(2+)](0) 2.0 mmol/L下，7.5 s- 2hz刺激组诱导DADs。添加或不添加100 μ mol/L链霉素时，BDM射流增强了DADs （n = 6, P < 0.05）和后收缩（n = 6, P < 0.05），并偶有动作电位。在最后一次刺激的列车抽搐期间，从2.0 μ m到2.1或2.2 μ m的拉伸脉冲加速Ca（2+）波，与拉伸力的增量成正比（P < 0.01），有或没有链霉素。在1 mmol/L咖啡因的作用下，拉伸脉冲后肌肉的快速缩短增加了BZ内的[Ca(2+)](i)，其幅度与拉伸力的增量相关（n = 15, P < 0.01）。结论非均匀性肌肉收缩可使钙（2+）与BZ内肌丝分离，从而引起诱发性心律失常。
Aims We examined whether non-uniform muscle contraction affects delayed afterdepolarizations (DADs) by dissociating Ca(2+) from myofilaments within the border zone (BZ) between contracting and stretched regions.Methods and results Force, sarcomere length (SL), membrane potential, and [Ca(2+)](i) dynamics were measured in 31 ventricular trabeculae from rat hearts. Non-uniform muscle contraction was produced by exposing a restricted region of muscle to a jet of solution containing 20 mmol/L 2,3-butanedione monoxime (BDM). DADs were induced by 7.5 s-2 Hz stimulus trains at an SL of 2.0 mu m (24 degrees C, [Ca(2+)](o) 2.0 mmol/L). The BDM jet enhanced DADs (n = 6, P < 0.05) and aftercontractions (n = 6, P < 0.05) with or without 100 mu mol/L streptomycin and occasionally elicited an action potential. A stretch pulse from an SL of 2.0 mu m to 2.1 or 2.2 mu m during the last stimulated twitch of the trains accelerated Ca(2+) waves in proportion to the increment of force by the stretch (P < 0.01) with or without streptomycin. In the presence of 1 mmol/L caffeine, rapid shortening of the muscle after the stretch pulse increased [Ca(2+)](i) within the BZ, whose amplitude correlated with the increment of force by the stretch (n = 15, P < 0.01).Conclusion These results suggest that non-uniform muscle contraction can enhance DADs by dissociating Ca(2+) from myofilaments within the BZ and thereby cause triggered arrhythmias.