Meyer M, Bluhm W F, He H, Post S R, Giordano F J, Lew W Y, Dillmann W H
Department of Medicine and Department of Pharmacology, University of California, San Diego, and Department of Medicine, Department of Veterans Affairs Medical Center, La Jolla, California 92093, USA.
Am J Physiol. 1999 Mar;276(3):H779-85. doi: 10.1152/ajpheart.1999.276.3.H779.
The force-frequency relationship (FFR) describes the frequency-dependent potentiation of cardiac contractility. The interaction of the sarcoplasmic reticulum Ca2+-adenosinetriphosphatase (SERCA2) with its inhibitory protein phospholamban (PLB) might be involved in the control of the FFR. The FFR was analyzed in two systems in which the PLB-to-SERCA2 ratio was modulated. Adult rabbit cardiac myocytes were transduced with adenovirus encoding for SERCA2, PLB, and beta-galactosidase (control). After 3 days, the relative PLB/SERCA2 values were significantly different between groups (SERCA2, 0.5; control, 1.0; PLB, 4.5). SERCA2 overexpression shortened relaxation by 23% relative to control, whereas PLB prolonged relaxation by 39% and reduced contractility by 47% (0.1 Hz). When the stimulation frequency was increased to 1.5 Hz, myocyte contractility was increased by 30% in control myocytes. PLB-overexpressing myocytes showed an augmented positive FFR (+78%), whereas SERCA2-transduced myocytes displayed a negative FFR (-15%). A more negative FFR was also found in papillary muscles from SERCA2 transgenic mice. These findings demonstrate that the ratio of phospholamban to SERCA2 is an important component in the control of the FFR.
力-频率关系（FFR）描述了心脏收缩力的频率依赖性增强。肌浆网Ca2+ -三磷酸腺苷酶（SERCA2）与其抑制性蛋白受磷蛋白（PLB）之间的相互作用可能参与了FFR的调控。在两个调节PLB与SERCA2比例的系统中分析了FFR。用编码SERCA2、PLB和β-半乳糖苷酶（对照）的腺病毒转导成年兔心肌细胞。3天后，各组之间相对PLB/SERCA2值有显著差异（SERCA2组为0.5；对照组为1.0；PLB组为4.5）。与对照组相比，SERCA2过表达使舒张期缩短23%，而PLB使舒张期延长39%，收缩力降低47%（0.1Hz）。当刺激频率增加到1.5Hz时，对照心肌细胞的收缩力增加30%。过表达PLB的心肌细胞显示出增强的正向FFR（+78%），而转导SERCA2的心肌细胞显示出负向FFR（-15%）。在SERCA2转基因小鼠的乳头肌中也发现了更负的FFR。这些发现表明，受磷蛋白与SERCA2的比例是FFR调控中的一个重要组成部分。
