Faculty of Life Sciences, University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK.
J Mol Cell Cardiol. 2010 May;48(5):917-24. doi: 10.1016/j.yjmcc.2010.02.008. Epub 2010 Feb 17.
Fish myocytes continue to develop active tension when stretched to sarcomere lengths (SLs) on the descending limb of the mammalian length-tension relationship. A greater length-dependent activation in fish than mammals could account for this because the increase in Ca(2+) sensitivity may overcome the tendency for force to fall due to reduced cross-bridge availability at SLs above optimal myofilament overlap. We stretched skinned fish and rat ventricular myocytes over a wide range of SLs, including those on the descending limb of the mammalian length-tension relationship. We found that fish myocytes developed greater active tension than rat myocytes at physiological Ca(2+) concentrations at long SLs as a result of a higher Ca(2+) sensitivity and a steeper relationship between Ca(2+) sensitivity and SL. We also investigated the diastolic properties of fish and rat myocytes at long SLs by measuring titin-based passive tension, titin isoform expression and titin phosphorylation. Fish myocytes produced higher titin-based passive tension despite expressing a higher proportion of a long N2BA-like isoform (38.0+/-2% of total vs 0% in rat). However, titin phosphorylation in fish myocytes was lower than in rat, which may explain some of the difference in passive tension between species. The high level of titin-based passive tension and the differential phosphorylation of sarcomeric proteins in fish myocytes may contribute to the enhanced length-dependent activation and underlie the extended range of in vivo stroke volumes found in fish compared with mammals.
当鱼类肌纤维被拉伸至哺乳动物张力-长度关系的下降支上的肌节长度 (SL) 时，它们会继续产生主动张力。鱼类比哺乳动物具有更大的长度依赖性激活，这可以解释为 Ca(2+) 敏感性的增加可能克服了由于在最佳肌丝重叠以上的 SL 上减少了横桥可用性而导致的力下降的趋势。我们在广泛的 SL 范围内拉伸了去皮的鱼类和大鼠心室肌纤维，包括哺乳动物张力-长度关系下降支上的 SL。我们发现，由于 Ca(2+) 敏感性较高和 Ca(2+) 敏感性与 SL 之间的关系更陡峭，鱼类肌纤维在生理 Ca(2+) 浓度下，在长 SL 上产生的主动张力大于大鼠肌纤维。我们还通过测量基于titin 的被动张力、titin 同工型表达和 titin 磷酸化来研究鱼类和大鼠肌纤维在长 SL 下的舒张特性。尽管鱼类表达了更高比例的长 N2BA 样同工型（38.0+/-2%，而大鼠中为 0%），但鱼类肌纤维产生的基于 titin 的被动张力更高。然而，鱼类肌纤维中的 titin 磷酸化低于大鼠，这可能解释了物种间被动张力差异的部分原因。鱼类肌纤维中基于 titin 的被动张力水平较高和肌节蛋白的磷酸化差异可能有助于增强长度依赖性激活，并为与哺乳动物相比鱼类体内冲程量的扩展范围提供基础。
