Altered cross-bridge characteristics following haemodynamic overload in rabbit hearts expressing V3 myosin

• Published in: The Journal of physiology 2001-10, Vol.536 (2), p.569-582
• Main Authors: Peterson, Jon N., Nassar, Rashid, Anderson, Page A. W., Alpert, Norman R.
• Format: Article
• Language: English
• Subjects: Animals; Cardiac Myosins - metabolism; Cross-Linking Reagents - metabolism; Hemodynamics - physiology; Hot Temperature; Hypertrophy, Right Ventricular - metabolism; Hypertrophy, Right Ventricular - physiopathology; Models, Biological; Myocardial Contraction - physiology; Myosin Light Chains - metabolism; Papillary Muscles - metabolism; Papillary Muscles - physiopathology; Pressure; Rabbits; Research Reports; Space life sciences; Stress, Mechanical; Troponin I - metabolism; Troponin T - metabolism; Ventricular Myosins - metabolism
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.2001.0569c.xd

Our goal in this study was to evaluate the effect of haemodynamic overload on cross-bridge (XBr) kinetics in the rabbit heart independently of myosin heavy chain (MHC) isoforms, which are known to modulate kinetics in small mammals. We applied a myothermal-mechanical protocol to isometrically contracting papillary muscles from two rabbit heart populations: (1) surgically induced right ventricular pressure overload (PO), and (2) sustained treatment with propylthiouracil (PTU). Both treatments resulted in a 100 % V 3 MHC profile. XBr force–time integral (FTI), evaluated during the peak of the twitch from muscle FTI and tension-dependent heat, was greater in the PO hearts (0.80 ± 0.10 versus 0.45 ± 0.05 pN s, means ± s.e.m. ., P = 0.01). Within the framework of a two-state XBr model, the PO XBr developed more force while attached (5.8 ± 0.9 versus 2.7 ± 0.3 pN), with a lower cycling rate (0.89 ± 0.10 versus 1.50 ± 0.14 s −1 ) and duty cycle (0.14 ± 0.03 versus 0.24 ± 0.02). Only the ventricular isoforms of myosin light chain 1 and 2 and cardiac troponin I (cTnI) were expressed, with no difference in cTnI phosphorylation between the PO and PTU samples. The troponin T (TnT) isoform compositions in the PO and PTU samples were significantly different ( P = 0.001), with TnT 2 comprising 2.29 ± 0.03 % in PO hearts versus 0.98 ± 0.01 % in PTU hearts of total TnT. This study demonstrates that MHC does not mediate dramatic alterations in XBr function induced by haemodynamic overload. Our findings support the likelihood that differences among other thick and thin filament proteins underlie these XBr alterations.