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钙离子(Ca2+)和横桥动力学在决定大鼠和豚鼠去表皮小梁中Ca2+激活和舒张最大速率方面的作用。

Roles of Ca2+ and crossbridge kinetics in determining the maximum rates of Ca2+ activation and relaxation in rat and guinea pig skinned trabeculae.

作者信息

Palmer S, Kentish J C

机构信息

Department of Pharmacology, United Medical and Dental Schools, St. Thomas's Hospital, London, UK.

出版信息

Circ Res. 1998 Jul 27;83(2):179-86. doi: 10.1161/01.res.83.2.179.

Abstract

We examined the influences of Ca2+ and crossbridge kinetics on the maximum rate of force development during Ca2+ activation of cardiac myofibrils and on the maximum rate of relaxation. Flash photolysis of diazo-2 or nitrophenyl-EGTA was used to produce a sudden decrease or increase, respectively, in [Ca2+] within Triton-skinned trabeculae from rat and guinea pig hearts (22 degrees C). Trabeculae from both species had similar Ca2+ sensitivities, suggesting that the rate of dissociation of Ca2+ from troponin C (k(off)) is similar in the 2 species. However, the rate of relaxation after diazo-2 photolysis was 5 times faster in the rat (16.1 +/- 0.9 s(-1), mean +/- SEM, n = 11) than in the guinea pig (2.99 +/- 0.26 s(-1), n = 7). This indicates that the maximum relaxation rate is limited by crossbridge kinetics rather than by k(off). The maximum rates of rapid activation by Ca2+ after nitrophenyl-EGTA photolysis (k(act)) and of force redevelopment after forcible crossbridge dissociation (k(act)) were similar and were approximately 5-fold faster in rat (k(act)= 14.4 +/- 0.9 s(-1), k(tr)= 13.0 +/- 0.6 s(-1)) than in guinea pig (k(act)= 2.57 +/- 0.14 s(-1), k(tr)= 2.69 +/- 0.30 s(-1)) trabeculae. This too may be mainly due to species differences in crossbridge kinetics. Both k(act) and k(tr) increased as [Ca2+] increased. This Ca2+ dependence of the rates of force development is consistent with current models for the Ca2+ activation of the crossbridge cycle, but these models do not explain the similarity in the maximal rates of activation and relaxation within a given species.

摘要

我们研究了钙离子(Ca2+)和横桥动力学对心肌肌原纤维Ca2+激活过程中最大力发展速率以及最大舒张速率的影响。利用重氮-2或硝基苯基乙二醇双乙酸酯(nitrophenyl-EGTA)的闪光光解作用,分别使来自大鼠和豚鼠心脏(22摄氏度)的经曲拉通处理的小梁内的[Ca2+]突然降低或升高。两个物种的小梁具有相似的Ca2+敏感性,这表明Ca2+从肌钙蛋白C上解离的速率(k(off))在这两个物种中相似。然而,重氮-2光解后的舒张速率在大鼠中(16.1±0.9 s(-1),平均值±标准误,n = 11)比在豚鼠中(2.99±0.26 s(-1),n = 7)快5倍。这表明最大舒张速率受横桥动力学限制而非k(off)。硝基苯基-EGTA光解后Ca2+快速激活的最大速率(k(act))以及强制横桥解离后力重新发展的最大速率(k(act))相似,并且在大鼠小梁中(k(act)= 14.4±0.9 s(-1),k(tr)= 13.0±0.6 s(-1))比在豚鼠小梁中(k(act)= 2.57±0.14 s(-1),k(tr)= 2.69±0.30 s(-1))快约5倍。这也可能主要归因于横桥动力学的物种差异。k(act)和k(tr)均随着[Ca2+]的增加而增加。力发展速率对Ca2+的这种依赖性与当前关于横桥循环Ca2+激活的模型一致,但这些模型无法解释给定物种内激活和舒张最大速率的相似性。

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