Frequency-dependent changes in contribution of SR Ca2+ to Ca2+ transients in failing human myocardium assessed with ryanodine.
Frequency-dependent changes in contribution of SR Ca2+ to Ca2+ transients in failing human myocardium assessed with ryanodine.
复制标题
用兰尼定评估衰竭的人类心肌中 SR Ca2 对 Ca2 瞬变的贡献的频率依赖性变化。
DOI：
10.1006/jmcc.1998.0690
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Pieske,B
中科院分区：
文献类型：
--
作者：
Schlotthauer,K;Schattmann,J;Bers,DM;Maier,LS;Schutt,U;Minami,K;Just,H;Hasenfuss,G;Pieske,B
我们检测了用ryanodine（1μm）阻断肌浆网（SR）功能对衰竭人心肌细胞内钙瞬变和颤搐力的刺激率依赖性变化的影响。使用来自10个终末期衰竭的人类心脏的心室的等距收缩、电刺激肌肉条。用细胞内Ca 2+指示剂水母发光蛋白加载肌肉。在0.5-3 Hz的刺激速率下，在ryanodine暴露（37°C）之前和之后同时记录细胞内Ca 2+瞬变和抽搐力。Ryanodine可显著降低衰竭心肌在1Hz时的收缩力（46±9%）和水母发光蛋白（57±10%）（P<0.05）。Ryanodine后，减弱或相反的水母发光蛋白光-频率关系变为正相关：在衰竭的人心肌中，Ryanodine前的收缩力和水母发光蛋白光不随频率的增加而增加，在3 Hz时，收缩力显著降低（P<0.05）。Ryanodine处理后，肌颤强度（P<0.05）和水母发光强度随刺激频率的增加而增加，在2 Hz时达到最大值。数据表明，SR功能的抑制显着降低收缩力和Ca 2+瞬变在失败的人心肌，但转换成一个积极的钝化或反向Ca 2+和力-频率关系。我们推断，在衰竭的人心肌中，负责50%的收缩力的Ca 2+来自SR，50%来自肌膜Ca 2+内流。这种肌膜成分在较高的刺激频率下增加。
We tested the influence of blocking sarcoplasmic reticulum (SR) function with ryanodine (1μm) on stimulation rate-dependent changes of intracellular Ca2+transients and twitch force in failing human myocardium. Isometrically contracting, electrically stimulated muscle strips from ventricles of 10 end-stage failing human hearts were used. Muscles were loaded with the intracellular Ca2+indicator aequorin. At stimulation rates from 0.5–3 Hz, intracellular Ca2+transients and twitch force were simultaneously recorded before and after ryanodine exposure (37°C). Ryanodine significantly reduced twitch force at 1 Hz by 46±9% and aequorin light by 57±10% in failing human myocardium (P<0.05). The blunted or inverse aequorin light– and force–frequency relation became positive after ryanodine: in failing human myocardium, twitch force and aequorin light before ryanodine did not increase with increasing frequency and force decreased significantly at 3 Hz (P<0.05). After ryanodine, twitch force (P<0.05) and aequorin light increased with increasing stimulation frequency and were maximum at 2 Hz. The data indicate that inhibition of SR function significantly reduces twitch force and Ca2+transients in failing human myocardium, but converts the blunted or inverse Ca2+– and force–frequency relation into a positive one. We infer that Ca2+responsible for 50% of twitch force is derived from the SR and 50% from sarcolemmal Ca2+influx in failing human myocardium. This sarcolemmal component increases at higher stimulation frequencies.