Relation between steady-state force and intracellular [Ca2+] in intact human myocardium. Index of myofibrillar responsiveness to Ca2+.
Relation between steady-state force and intracellular [Ca2+] in intact human myocardium. Index of myofibrillar responsiveness to Ca2+.
复制标题
完整人心肌中稳态力与细胞内 [Ca2] 之间的关系。
DOI:
10.1161/01.cir.82.4.1266
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发表时间:
1990
期刊:
影响因子:
37.8
通讯作者:
Hajjar,RJ
中科院分区:
文献类型:
--
作者:
Gwathmey,JK;Hajjar,RJ
A novel approach was developed allowing the measurement of steady-state force and intracellular calcium concentration ([Ca2+]i) in tetanized human ventricular trabeculae carneae without pharmacological intervention. We compared and contrasted three methods of assessing calcium sensitivity of the myofilaments: 1) force-[Ca2+] relations in skinned fiber preparations, 2) peak twitch force-peak [Ca2+]i relations, and 3) steady-state force-[Ca2+]i relations in intact muscles. Steady-state contractile activation was achieved rapidly by tetanizing intact human trabeculae, loaded with aequorin, a Ca2(+)-sensitive bioluminescent protein, at a stimulation frequency of 15-20 Hz. Steady-state force and [Ca2+]i were measured during tetani, and the force versus [Ca2+]i relation was obtained by varying the extracellular calcium concentration ([Ca2+]o). Force-[Ca2+]i relations obtained from control and myopathic hearts were fitted to the Hill equation: %Force = [Ca2+]inh/([Ca2+]inh50% + [Ca2+]inh), where nh is the Hill coefficient, and [Ca2+]50% is the [Ca2+] required for 50% activation. The curves of tetani had Hill coefficients of 5.21 +/- 0.20 (n = 6) and 5.61 +/- 0.60 (n = 10) and [Ca2+]50% of 0.56 +/- 0.05 microM (n = 6) and 0.54 +/- 0.09 microM (n = 10) in control and myopathic muscles, respectively. We also constructed peak force-peak [Ca2+]i relations using isometric twitches from the same muscles. These curves were shifted toward higher [Ca2+]i compared with the steady-state force-[Ca2+]i curve derived from tetani. Ryanodine (1 microM), which increased the time course of the Ca2+ and force transients, shifted the peak force-peak [Ca2+]i relation to the left, without affecting the steady-state force-[Ca2+]i relation. Exposure to 10 mM caffeine shifted the steady-state force-[Ca2+]i relation to the left, whereas exposure to 3 microM isoproterenol shifted this relation to the right. Experiments using skinned fiber preparations were performed in parallel with experiments on intact muscles from the same hearts. The force-pCa (-log[Ca2+]) relations in saponin-skinned trabeculae from control and myopathic tissue were superimposable. Ryanodine (1 microM) had no effect on the force-pCa relation in skinned fibers. Maximal tension was evoked by the posttetanic twitch, which was larger than the tetanus. This potentiation was abolished in the presence of ryanodine, a sarcoplasmic reticulum inhibitor. We propose that the changes in the steady-state force-[Ca2+]i relations are correlated with alterations in the sensitivity of the myofilaments to Ca2+, whereas changes in the peak force-peak [Ca2+]i relations represent temporal changes in the twitch transient.(ABSTRACT TRUNCATED AT 400 WORDS)
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DOI:
--
发表时间:
1987
期刊:
The Journal of General Physiology
影响因子:
--
作者:
R. Ventura;H. Mekhfi;G. Vassort
通讯作者:
G. Vassort
影响因子:
20.1
作者:
D. Maughan;E. Low;R. Litten;J. Brayden;Norman Axpert
通讯作者:
Norman Axpert
影响因子:
3.4
作者:
CANNELL, MB;ALLEN, DG
通讯作者:
ALLEN, DG
DOI:
10.1113/jphysiol.1981.sp013580
发表时间:
1981-02
期刊:
The Journal of Physiology
影响因子:
--
作者:
F. Julian;R. Moss
通讯作者:
F. Julian;R. Moss
影响因子:
20.1
作者:
E. Marbán;H. Kusuoka;D. T. Yue;M. Weisfeldt;W. Wier
通讯作者:
W. Wier