Impact of beta-myosin heavy chain isoform expression on cross-bridge cycling kinetics

• Published in: American journal of physiology. Heart and circulatory physiology 2005-02, Vol.288 (2), p.H896-H903
• Main Authors: Rundell, Veronica L M, Manaves, Vlasios, Martin, Anne F, de Tombe, Pieter P
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; Antithyroid Agents - pharmacology; Hypothyroidism - metabolism; Hypothyroidism - physiopathology; Isomerism; Kinetics; Male; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Myocytes, Cardiac - metabolism; Myosin Heavy Chains - chemistry; Myosin Heavy Chains - metabolism; Propylthiouracil - pharmacology; Rats; Rats, Inbred Lew; Ventricular Myosins - chemistry; Ventricular Myosins - metabolism
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00407.2004

Myosin heavy chain (MHC) isoforms alpha and beta have intrinsically different ATP hydrolysis activities (ATPase) and therefore cross-bridge cycling rates in solution. There is considerable evidence of altered MHC expression in rodent cardiac disease models; however, the effect of incremental beta-MHC expression over a wide range on the rate of high-strain, isometric cross-bridge cycling is yet to be ascertained. We treated male rats with 6-propyl-2-thiouracil (PTU; 0.8 g/l in drinking water) for short intervals (6, 11, 16, and 21 days) to generate cardiac MHC patterns in transition from predominantly alpha-MHC to predominantly beta-MHC. Steady-state calcium-dependent tension development and tension-dependent ATP consumption (tension cost; proportional to cross-bridge cycling) were measured in chemically permeabilized (skinned) right ventricular muscles at 20 degrees C. To assess dynamic cross-bridge cycling kinetics, the rate of force redevelopment (ktr) was determined after rapid release-restretch of fully activated muscles. MHC isoform content in each experimental muscle was measured by SDS-PAGE and densitometry. alpha-MHC content decreased significantly and progressively with length of PTU treatment [68 +/- 5%, 58 +/- 4%, 37 +/- 4%, and 27 +/- 6% for 6, 11, 16, and 21 days, respectively; P < 0.001 (ANOVA)]. Tension cost decreased, linearly, with decreased alpha-MHC content [6.7 +/- 0.4, 5.6 +/- 0.5, 4.0 +/- 0.4, and 3.9 +/- 0.3 ATPase/tension for 6, 11, 16, and 21 days, respectively; P < 0.001 (ANOVA)]. Likewise, ktr was significantly and progressively depressed with length of PTU treatment [11.1 +/- 0.6, 9.1 +/- 0.5, 8.2 +/- 0.7, and 6.2 +/- 0.3 s(-1) for 6, 11, 16, and 21 days, respectively; P < 0.05 (ANOVA)] Thus cross-bridge cycling, under high strain, for alpha-MHC is three times higher than for beta-MHC. Furthermore, under isometric conditions, alpha-MHC and beta-MHC cross bridges hydrolyze ATP independently of one another.