Rate of tension redevelopment is not modulated by sarcomere length in permeabilized human, murine, and porcine cardiomyocytes
Rate of tension redevelopment is not modulated by sarcomere length in permeabilized human, murine, and porcine cardiomyocytes
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DOI：
10.1152/ajpregu.00537.2006
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发表时间：
2007-07-01
影响因子：
2.8
通讯作者：
Papp, Zoltan
中科院分区：
文献类型：
--
作者：
Edes, Istvan Ferenc;Czuriga, Daniel;Papp, Zoltan
随着肌节长度(SL)的增加，等长力发育的钙敏感性增加被认为是心脏Frank-Starling定律的基础，可能涉及跨桥翻转动力学的调节。因此，在不同的SLS(1.9和2.3微米)下，我们测定了人、鼠和猪三种体外通透性心肌细胞的等长力产生和跨桥敏感的力再发展速率常数(k(Tr))对钙离子的依赖性。在10 mM无机磷酸盐(PI)存在下，K(Tr)也被测定，这干扰了力产生的跨桥转变。在人、小鼠和猪的心肌细胞中，SL增加的钙敏感性非常相似(Delta PCA(50)：类似于0.11)。在所有钙离子浓度([Ca~(2+)])[最大k(Tr)(k(tr，max))]下，小鼠的K(Tr)均高于人或猪(P<；0.05)，人、小鼠和猪的pCA4.75分别为1.33+/-0.11、7.44+/-0.15和1.02+/-0.05 S(-1)，但k(Tr)不依赖于任何物种的SL。此外，当每个物种的k(Tr)值相对于它们各自的最大值表示时，得到了类似的钙依赖关系。在所有三个物种中，10毫摩尔的PI使力降低到类似于60%-65%，并且保留Delta PCA(50)不变。PI使人和猪的k(tr，max)增加了约1.6倍，小鼠的k(tr，max)增加了约3倍，与SL无关。总而言之，物种差异对k(Tr)有主要影响，但SL似乎不调节人、小鼠和猪心脏的跨桥周转率。
The increase in Ca2+ sensitivity of isometric force development along with sarcomere length (SL) is considered as the basis of the Frank-Starling law of the heart, possibly involving the regulation of cross-bridge turnover kinetics. Therefore, the Ca2+ dependencies of isometric force production and of the cross-bridge-sensitive rate constant of force redevelopment (k(tr)) were determined at different SLs (1.9 and 2.3 mu m) in isolated human, murine, and porcine permeabilized cardiomyocytes. k(tr) was also determined in the presence of 10 mM inorganic phosphate (Pi), which interfered with the force-generating cross-bridge transitions. The increases in Ca2+ sensitivities of force with SL were very similar in human, murine, and porcine cardiomyocytes (Delta pCa(50): similar to 0.11). k(tr) was higher (P < 0.05) in mice than in humans or pigs at all Ca2+ concentrations ([Ca2+]) [maximum k(tr) (k(tr,max)) at a SL of 1.9 mu m and pCa 4.75: 1.33 +/- 0.11, 7.44 +/- 0.15, and 1.02 +/- 0.05 s(-1), in humans, mice, and pigs, respectively] but k(tr) did not depend on SL in any species. Moreover, when the k(tr) values for each species were expressed relative to their respective maxima, similar Ca2+ dependencies were obtained. Ten millimolar Pi decreased force to similar to 60-65% and left Delta pCa(50) unaltered in all three species. Pi increased k(tr,max) by a factor of similar to 1.6 in humans and pigs and by a factor of similar to 3 in mice, independent of SL. In conclusion, species differences exert a major influence on k(tr) but SL does not appear to modulate the cross-bridge turnover rates in human, murine, and porcine hearts.