title: Titin isoform variance and length dependence of activation in skinned bovine cardiac muscle.
abstract: We have explored the role of the giant elastic protein titin in the Frank-Starling mechanism of the heart by measuring the sarcomere length (SL) dependence of activation in skinned cardiac muscles with different titin-based passive stiffness characteristics. We studied muscle from the bovine left ventricle (BLV), which expresses a high level of a stiff titin isoform, and muscle from the bovine left atrium (BLA), which expresses more compliant titin isoforms. Passive tension was also varied in each muscle type by manipulating the pre-history of stretch prior to activation. We found that the SL-dependent increases in Ca2+ sensitivity and maximal Ca2+-activated tension were markedly more pronounced when titin-based passive tension was high. Small-angle X-ray diffraction experiments revealed that the SL dependence of reduction of interfilament lattice spacing is greater in BLV than in BLA and that the lattice spacing is coupled with titin-based passive tension. These results support the notion that titin-based passive tension promotes actomyosin interaction by reducing the lattice spacing. This work indicates that titin may be a factor involved in the Frank-Starling mechanism of the heart by promoting actomyosin interaction in response to stretch.
authors.affiliation: Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-6520, USA.
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: D000465:Algorithms; D000818:Animals; D002417:Cattle; D064211:Connectin; D004591:Electrophoresis, Polyacrylamide Gel; D006321:Heart / Q000502:physiology*; D006325:Heart Atria / Q000166:cytology; D006352:Heart Ventricles / Q000166:cytology; D066298:In Vitro Techniques; D007536:Isomerism; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D012518:Sarcomeres / Q000502:physiology / Q000648:ultrastructure; D016276:Ventricular Function; D014961:X-Ray Diffraction
chemical_list: D064211:Connectin; D009124:Muscle Proteins; D011494:Protein Kinases