Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, PC200
Skinned fish cardiomyocytes demonstrate an enhanced length-dependent Ca2+ activation.
S. M. Patrick1, A. C. Hoskins2, J. C. Kentish2, E. White3, H. A. Shiels1, O. Cazorla4
1. Life Sciences, The University of Manchester, Manchester, United Kingdom. 2. Cardiovascular Division, King?
Fish myocytes continue to develop active tension when stretched to sarcomere lengths (SLs) on the descending limb of the mammalian length-tension relationship (Shiels et al. 2006). A greater length-dependent activation in fish than mammals could account for this, since the increase in Ca2+ 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 Ca2+ concentrations at long SL. This was due to a higher Ca2+ sensitivity and a steeper relationship between Ca2+ sensitivity and SL in the fish myocytes. The greatest difference in Ca2+ sensitivity was found at the longest SL (2.7 µm), where pCa50 for the rat myocytes was 6.19 ± 0.07 pCa units compared with 6.54 ± 0.03 for fish myocytes (p < 0.05, One-way ANOVA with Student-Newman-Keul’s post-hoc, n = 6-8). 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, n = 4). 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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