title: Enhanced length-dependent Ca2+ activation in fish cardiomyocytes permits a large operating range of sarcomere lengths.
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 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.
authors.affiliation: Faculty of Life Sciences, University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Patrick
authors.forename: Anita C
authors.initials: AC
authors.lastname: Hoskins
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Kentish
authors.forename: Ed
authors.initials: E
authors.lastname: White
authors.forename: Holly A
authors.initials: HA
authors.lastname: Shiels
authors.forename: Olivier
authors.initials: O
authors.lastname: Cazorla
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D064211:Connectin; D005399:Fishes; D009124:Muscle Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D012518:Sarcomeres / Q000378:metabolism*; D000099163:Myosin Binding Protein C
chemical_list: D002118:Calcium; D002352:Carrier Proteins; D064211:Connectin; D009124:Muscle Proteins; D018994:Myosin Light Chains; D011494:Protein Kinases; D000099163:Myosin Binding Protein C