title: Impact of osmotic compression on sarcomere structure and myofilament calcium sensitivity of isolated rat myocardium.
abstract: Changes in interfilament lattice spacing have been proposed as the mechanism underlying myofilament length-dependent activation. Much of the evidence to support this theory has come from experiments in which high-molecular-weight compounds, such as dextran, were used to osmotically shrink the myofilament lattice. However, whether interfilament spacing directly affects myofilament calcium sensitivity (EC(50)) has not been established. In this study, skinned isolated rat myocardium was osmotically compressed over a wide range (Dextran T500; 0-6%), and EC(50) was correlated to both interfilament spacing and I(1,1)/I(1,0) intensity ratio. The latter two parameters were determined by X-ray diffraction in a separate group of skinned muscles. Osmotic compression induced a marked reduction in myofilament lattice spacing, concomitant with increases in both EC(50) and I(1,1)/I(1,0) intensity ratio. However, interfilament spacing was not well correlated with EC(50) (r(2) = 0.78). A much better and deterministic relationship was observed between EC(50) and the I(1,1)/I(1,0) intensity ratio (r(2) = 0.99), albeit with a marked discontinuity at low levels of dextran compression; that is, a small amount of external osmotic compression (0.38 kPa, corresponding to 1% Dextran T500) produced a stepwise increase in the I(1,1)/I(1,0) ratio concomitant with a stepwise decrease in EC(50). These parameters then remained stable over a wide range of further applied osmotic compression (up to 6% dextran). These findings provide support for a "switch-like" activation mechanism within the cardiac sarcomere that is highly sensitive to changes in external osmotic pressure.
authors.affiliation: Dept. of Physiology and Biophysics M/C 901, Univ. of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612, USA. farman@uic.edu
authors.forename: Gerrie P
authors.initials: GP
authors.lastname: Farman
authors.forename: John S
authors.initials: JS
authors.lastname: Walker
authors.forename: Pieter P
authors.initials: PP
authors.lastname: de Tombe
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Irving
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000494:pharmacology*; D003911:Dextrans / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009997:Osmotic Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D012518:Sarcomeres / Q000502:physiology* / Q000648:ultrastructure*; D014961:X-Ray Diffraction
chemical_list: D003911:Dextrans; D002118:Calcium