title: Titin-based modulation of active tension and interfilament lattice spacing in skinned rat cardiac muscle.
abstract: The effect of titin-based passive tension on Ca2+ sensitivity of active tension and interfilament lattice spacing was studied in skinned rat ventricular trabeculae by measuring the sarcomere length (SL)-dependent change in Ca2+ sensitivity and performing small angle X-ray diffraction studies. To vary passive tension, preparations were treated with trypsin at a low concentration (0.31 mug/ml) for a short period (13 min) at 20 degrees C, that resulted in approximately 40% degradation of the I-band region of titin, with a minimal effect on A-band titin. We found that the effect of trypsin on titin-based passive tension was significantly more pronounced immediately after stretch than at steady state, 30 min after stretch (i.e., trypsin has a greater effect on viscosity than on elasticity of passive cardiac muscle). Ca2+ sensitivity was decreased by trypsin treatment at SL 2.25 microm, but not at SL 1.9 microm, resulting in marked attenuation of the SL-dependent increase in Ca2+ sensitivity. The SL-dependent change in Ca2+ sensitivity was significantly correlated with titin-based passive tension. Small-angle X-ray diffraction experiments revealed that the lattice spacing expands after trypsin treatment, especially at SL 2.25 microm, providing an inverse linear relationship between the lattice spacing and Ca2+ sensitivity. These results support the view that titin-based passive tension promotes actomyosin interaction and that the mechanism includes interfilament lattice spacing modulation.
authors.affiliation: Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA, 99164-6520, USA. noriof@jikei.ac.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Fukuda
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wu
authors.forename: Gerrie
authors.initials: G
authors.lastname: Farman
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Irving
authors.forename: Henk
authors.initials: H
authors.lastname: Granzier
mesh_terms: D000205:Actomyosin / Q000737:chemistry / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D064211:Connectin; D066298:In Vitro Techniques; D009124:Muscle Proteins / Q000737:chemistry / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*; D011494:Protein Kinases / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D012518:Sarcomeres / Q000502:physiology*; D014357:Trypsin / Q000494:pharmacology; D014961:X-Ray Diffraction
chemical_list: D064211:Connectin; D009124:Muscle Proteins; D000205:Actomyosin; D011494:Protein Kinases; D014357:Trypsin; D002118:Calcium