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Enhanced length-dependent Ca2+ activation in fish cardiomyocytes permits a large operating range of sarcomere lengths

Abstract : Length-tension relationship Skinned cardiac myocytes Phosphorylation Myosin binding protein C (MyBPC) Myosin light chain-2 (MLC-2) TnI TnT 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.
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Simon Patrick, Anita Hoskins, Jonathan Kentish, Ed White, Holly Shiels, et al.. Enhanced length-dependent Ca2+ activation in fish cardiomyocytes permits a large operating range of sarcomere lengths. Journal of Molecular and Cellular Cardiology, Elsevier, 2010, 48 (5), pp.917 - 924. ⟨10.1016/j.yjmcc.2010.02.008⟩. ⟨hal-01824348⟩

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