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

Simon M. Patrick, Anita C. Hoskins, Jonathan C. Kentish, Ed White, Holly A. Shiels, Olivier Cazorla

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

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 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 SLs as a result of a higher Ca2+ sensitivity and a steeper relationship between Ca2+ 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 +/- 28 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. (C) 2010 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)917 - 924
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume48
Issue number5
DOIs
Publication statusPublished - May 2010

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