Myofilament Calcium Sensitivity in Skinned Rat Cardiac Trabeculae

John P. Konhilas, Thomas C. Irving, Pieter P. de Tombe
2002 Circulation Research  
The increase in myofilament Ca 2ϩ responsiveness on an increase in sarcomere length (SL) is, in part, the cellular basis for Frank-Starling's law of the heart. It has been suggested that a decrease in myofilament lattice spacing (LS) in response to an increase in SL underlies this phenomenon. This hypothesis is supported by previous studies in which reduced muscle width induced by osmotic compression was associated with an increase in Ca 2ϩ sensitivity, mimicking those changes observed with an
more » ... ncrease in SL. To evaluate this hypothesis, we directly measured LS by synchrotron x-ray diffraction as function of SL in skinned rat cardiac trabeculae bathed in 0% to 6% dextran solutions (MW 413 000). We found that EC 50 , [Ca 2ϩ ] at which force is half-maximal, at SL between 1.95 and 2.25 m did not vary in proportion to LS when 3% or 6% dextran solutions were applied. We also found that moderate compression (1% dextran) of skinned trabeculae at SLϭ2.02 m reduced LS (LSϭ42.29Ϯ0.14 nm) to match that of uncompressed fibers at a long SL (SLϭ2.19 m; LSϭ42.28Ϯ0.15 nm). Whereas increasing SL from 2.02 to 2.19 m significantly increased Ca 2ϩ sensitivity as indexed by the EC 50 parameter (2.87Ϯ0.11 mol/L to 2.52Ϯ0.12 mol/L), similar reduction in myofilament lattice spacing achieved by compression with 1% dextran did not alter Ca 2ϩ sensitivity (2.87Ϯ0.10 mol/L) at the short SL. We conclude that alterations in myofilament lattice spacing may not be the mechanism that underlies the sarcomere length-induced alteration of calcium sensitivity in skinned myocardium. (Circ Res. 2002;90: 59-65.)
doi:10.1161/hh0102.102269 pmid:11786519 fatcat:pn2htip4fbhujmf2vpkzcr7uiq