频率依赖性力产生与人心肌中的肌浆网钙ATP酶活性相关。

Frequency dependent force generation correlates with sarcoplasmic calcium ATPase activity in human myocardium.

作者信息

Frank K, Bölck B, Bavendiek U, Schwinger R H

机构信息

Klinik III für Innere Medizin der Universität zu Köln.

出版信息

Basic Res Cardiol. 1998 Oct;93(5):405-11. doi: 10.1007/s003950050109.

DOI:10.1007/s003950050109

PMID:9833153

Abstract

OBJECTIVE

In congestive heart failure both a decreased function of the sarcoplasmic Ca(2+)-ATPase and a negative force-frequency relationship have been shown. This study aimed to investigate a possible relationship between frequency potentiation, sarcoplasmic Ca(2+)-ATPase activity, and SERCA2 protein expression in human myocardium.

METHODS

Frequency potentiation was studied in electrically stimulated, isometric, left ventricular papillary muscle strip preparations (37 degrees C, 0.5-3.0 Hz) from terminally failing (NYHA i.v.; n = 5, dilated cardiomyopathy) and nonfailing (donor hearts, n = 5) human myocardium. In the identical samples the Ca(2+)-ATPase activity (NADH coupled assay) and the protein expression of sarcoplasmic Ca(2+)-ATPase (SERCA2), phospholamban, and calsequestrin (western blot) were determined. The frequency dependent change in the force of contraction and Vmax of the Ca(2+)-ATPase activity and the protein expression of SERCA2 were correlated with each other.

RESULTS

In terminally failing myocardium the force-frequency relationship was negative (2.0 Hz vs. 0.5 Hz: -0.2 +/- 0.1 delta mN) contrasting a positive rate dependent potentiation of force in nonfailing tissue (2.0 Hz vs. 0.5 Hz: +0.8 +/- 0.2 delta mN; p < 0.01). In failing myocardium the corresponding maximal sarcoplasmic Ca(2+)-ATPase activity (Vmax) was reduced significantly compared to nonfailing myocardium (174 +/- 24 vs. 296 +/- 31 nmol ATP/mg.min, p < 0.01). The protein expression of SERCA2, phospholamban, and calsequestrin remained unchanged in failing myocardium. The maximal Ca(2+)-ATPase activity significantly correlated with the frequency dependent change in force of contraction (2 Hz vs. 0.5 Hz: r = 0.88, p = 0.001; 3 Hz vs. 0.5 Hz: r = 0.84, p = 0.004). No correlation between protein expression of SERCA2 and Ca(2+)-ATPase activity or change in force of contraction was observed.

CONCLUSION

Due to a significant correlation between sarcoplasmic Ca(2+)-ATPase activity and frequency potentiation, the negative rate dependent force potentiation in human heart failure could be at least in part be attributed to decreased function of the sarcoplasmic Ca(2+)-ATPase.

摘要

目的

在充血性心力衰竭中，肌浆网Ca(2+)-ATP酶功能降低以及负性力-频率关系均已得到证实。本研究旨在探讨频率增强、肌浆网Ca(2+)-ATP酶活性和人心肌中SERCA2蛋白表达之间的可能关系。

方法

在来自终末期衰竭（纽约心脏协会心功能IV级；n = 5，扩张型心肌病）和非衰竭（供体心脏，n = 5）人心脏的经电刺激的等长左心室乳头肌条标本（37℃，0.5 - 3.0Hz）中研究频率增强。在相同样本中测定Ca(2+)-ATP酶活性（NADH偶联测定法）以及肌浆网Ca(2+)-ATP酶（SERCA2）、受磷蛋白和肌集钙蛋白的蛋白表达（蛋白质印迹法）。收缩力的频率依赖性变化、Ca(2+)-ATP酶活性的Vmax以及SERCA2的蛋白表达相互关联。

结果

在终末期衰竭心肌中，力-频率关系为负性（2.0Hz对0.5Hz：-0.2±0.1ΔmN），这与非衰竭组织中力的正性频率依赖性增强形成对比（2.0Hz对0.5Hz：+0.8±0.2ΔmN；p < 0.01）。与非衰竭心肌相比，衰竭心肌中相应的最大肌浆网Ca(2+)-ATP酶活性（Vmax）显著降低（174±24对296±31nmol ATP/mg·min，p < 0.01）。在衰竭心肌中，SERCA2、受磷蛋白和肌集钙蛋白的蛋白表达保持不变。最大Ca(2+)-ATP酶活性与收缩力的频率依赖性变化显著相关（2Hz对0.5Hz：r = 0.88，p = 0.00；3Hz对0.5Hz：r = 0.84，p = 0.004）。未观察到SERCA2的蛋白表达与Ca(2+)-ATP酶活性或收缩力变化之间的相关性。