Anti-C. tetani Polyclonal antibody

The goal of this study was to determine whether Ca2+ plays a role in regulating tension development kinetics in intact cardiac muscle. In cardiac muscle, this fundamental issue of Ca2+ regulation has been controversial. The approach was to induce steady-state tetanic contractions of intact right ventricular trabeculae from rat hearts at varying external Ca2+ concentrations ([Ca2+]) at 22 degrees C. During tetani, cross bridges were mechanically disrupted and the kinetics of tension redevelopment were assessed from the rate constant of exponential tension redevelopment (k(tr)). There was a relationship between ht, and external [Ca2+] that was similar in form to the relationship between tension and [Ca2+]. Thus a close relationship also existed between k(tr) and tension (r = 0.88; P < 0.001); whereas at maximal tetanic tension (saturating cytosolic [Ca2+]), k(tr) was 16.4 +/- 2.2 s(-1) (mean +/- SE, n = 7), at zero tension (low cytosolic [Ca2+]), k(tr) extrapolated to 20% of maximum (3.3 +/- 0.7 s(-1)). Qualitatively similar results were obtained using different mechanical protocols to disrupt cross bridges. These data demonstrate that tension redevelopment kinetics in intact cardiac muscle are influenced by the level of Ca2+ activation. These findings contrast with the findings of one previous study of intact cardiac muscle. Activation dependence of tension development kinetics may play an important role in determining the rate and extent of myocardial tension rise during the cardiac cycle in vivo.

The effects of the general antioxidant N-acetylcysteine (NAC) on muscle function and metabolism were examined. Isolated paired mouse extensor digitorum longus muscles were studied in the absence or presence of 20 mM NAC. Muscles were electrically stimulated to perform 100 isometric tetanic contractions (300 ms duration) at frequencies resulting in similar to 85 % of maximal force (70-150 Hz at 25-40 A degrees C). NAC did not significantly affect peak force in the unfatigued state at any temperature but significantly slowed tetanic force development in a temperature-dependent fashion (e.g., time to 50 % of peak tension averaged 35 A +/- 2 ms [control] and 37 A +/- 1 ms [NAC] at 25 A degrees C vs. 21 A +/- 1 ms [control] and 52 A +/- 6 ms [NAC, P < 0.01] at 40 A degrees C). During repeated contractions, NAC maximally enhanced peak force by the fifth tetanus at all temperatures (by similar to 30 %). Thereafter, the effect of NAC disappeared rapidly at high temperatures (35-40 A degrees C) and more slowly at the lower temperatures (25-30 A degrees C). At all temperatures, the enhancing effect of NAC on peak force was associated with a slowing of relaxation. NAC did not significantly affect myosin light chain phosphorylation at rest or after five contractions (similar to 50 % increase vs. rest). After five tetani, lactate and inorganic phosphate increased about 20-fold and 2-fold, respectively, both in control and NAC-treated muscles. Interestingly, after five tetani, the increase in glucose 6-P was similar to 2-fold greater, whereas the increase in malate was inhibited by similar to 75 % with NAC vs. control, illustrating the metabolic effects of NAC. NAC slightly decreased the maximum shortening velocity in early fatigue (five to seven repeated tetani). These data demonstrate that the antioxidant NAC transiently enhances muscle force generation by a mechanism that is independent of changes in myosin light chain phosphorylation and inorganic phosphate. The slowing of relaxation suggests that NAC enhances isometric force by facilitating fusion (i.e., delaying force decline between pulses). The initial slowing of tension development and subsequent slowing of relaxation suggest that NAC would result in impaired performance during a high-intensity dynamic exercise.