title: Insights into length-dependent regulation of cardiac cross-bridge cycling kinetics in human myocardium.
abstract: Cross-bridge cycling kinetics play an essential role in the heart's ability to contract and relax. The rate of tension redevelopment (ktr) slows down as a muscle length is increased in intact human myocardium. We set out to determine the effect of rapid length step changes and protein kinase A (PKA) and protein kinase C-βII (PKC-βII) inhibitors on the ktr in ultra-thin non-failing and failing human right ventricular trabeculae. After stabilizing the muscle either at L90 (90% of optimal length) or at Lopt (optimal length), we rapidly changed the length to either Lopt or L90 and measured ktr. We report that length-dependent changes in ktr occur very rapidly (in the order of seconds or faster) in both non-failing and failing muscles and that the length at which a muscle had been stabilized prior to the length change does not significantly affect ktr. In addition, at L90 and at Lopt, PKA and PKC-βII inhibitors did not significantly change ktr. Our results reveal that length-dependent regulation of cross-bridge cycling kinetics predominantly occurs rapidly and involves the intrinsic properties of the myofilament rather than post-translational modifications that are known to occur in the cardiac muscle as a result of a change in muscle/sarcomere length.
authors: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, USA; Medical Scientist Training Program and Biomedical Sciences Graduate Program, The Ohio State University Wexner Medical Center, USA.
authors: Nima
authors: N
authors: Milani-Nejad
authors: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, USA; Medical Scientist Training Program and Biomedical Sciences Graduate Program, The Ohio State University Wexner Medical Center, USA.
authors: Jae-Hoon
authors: JH
authors: Chung
authors: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, USA.
authors: Benjamin D
authors: BD
authors: Canan
authors: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, USA.
authors: Jonathan P
authors: JP
authors: Davis
authors: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, USA.
authors: Vadim V
authors: VV
authors: Fedorov
authors: Department of Surgery, Division of Cardiac Surgery, The Ohio State University Wexner Medical Center, USA.
authors: Robert S D
authors: RS
authors: Higgins
authors: Department of Surgery, Division of Cardiac Surgery, The Ohio State University Wexner Medical Center, USA.
authors: Ahmet
authors: A
authors: Kilic
authors: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, USA; Department of Internal Medicine, The Ohio State University Wexner Medical Center, USA.
authors: Peter J
authors: PJ
authors: Mohler
authors: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, USA; Department of Internal Medicine, The Ohio State University Wexner Medical Center, USA. Electronic address: janssen.10@osu.edu.
authors: Paul M L
authors: PM
authors: Janssen
mesh_terms: D000328:Adult; D000368:Aged; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005260:Female; D006321:Heart / Q000502:physiology*; D006333:Heart Failure / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000502:physiology*; D064546:Protein Kinase C beta / Q000037:antagonists & inhibitors; D012518:Sarcomeres / Q000502:physiology*; D015398:Signal Transduction; D013449:Sulfonamides / Q000737:chemistry
chemical_list: D007546:Isoquinolines; D013449:Sulfonamides; D017868:Cyclic AMP-Dependent Protein Kinases; D064546:Protein Kinase C beta; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: Cross-bridge cycling kinetics; Muscle length; Post-translational modification; Rate of tension redevelopment; Trabeculae