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

J Mol Cell Cardiol. 2010 May;48(5):917-24. doi: 10.1016/j.yjmcc.2010.02.008. Epub 2010 Feb 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Carrier Proteins / metabolism
  • Connectin
  • Fishes
  • Muscle Proteins / metabolism
  • Myocytes, Cardiac / metabolism*
  • Myosin Light Chains / metabolism
  • Phosphorylation
  • Protein Kinases / metabolism
  • Rats
  • Sarcomeres / metabolism*

Substances

  • Carrier Proteins
  • Connectin
  • Muscle Proteins
  • Myosin Light Chains
  • myosin-binding protein C
  • Protein Kinases
  • Calcium