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

被引:78
作者
Palmer, S [1 ]
Kentish, JC [1 ]
机构
[1] St Thomas Hosp, UMDS, Dept Pharmacol, London SE1 7EH, England
关键词
crossbridge; photolysis; Ca2+ activation; cardiac myofibril; relaxation;
D O I
10.1161/01.RES.83.2.179
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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(tr)) were similar and were approximate to 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.
引用
收藏
页码:179 / 186
页数:8
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