Acting on an impulse (or two): Advantages of high-frequency tetanic onset in skeletal muscle

Abstract

Moss et al. highlight why high-frequency bursts at the onset of tetany increase force development in fast-twitch skeletal muscle fibers.

Figure 1.

Effects of a strong binding derivative of myosin subfragment-1 (NEM-S1) on the rate constant of force development in rabbit permeabilized, fast-twitch, skeletal muscle fibers. See Fitzsimons et al. (2001). Control: The rate of force development increases by nearly an order of magnitude when the level of activation with Ca²⁺ is increased from near threshold (P/P₀ = 0) to saturating (P/P₀ = 1.0) for force development. NEM-S1: Infusion of a strong binding, nonforce-generating derivative of myosin subfragment-1 (N-ethylmaleimide-modified S1, or NEM-S1) speeds the rate of force development at submaximal concentrations of Ca²⁺ (P/P₀ < 1.0). The acceleration of force development is caused by increased cooperative binding of myosin to actin as a result of the binding of NEM-S1 to actin, displacement of the Tn/Tm regulatory strand, and increased cross-bridge binding to the thin filament. The acceleration of force development is greater at higher concentrations of NEM-S1 because of greater displacement of the regulatory strand. NEM-S1 has virtually no effect at maximal activation (P/P₀ = 1.0) because the Tn/Tm regulatory strand is already fully displaced and the thin filament maximally activated due to the saturation of Ca²⁺ binding to troponin C. Methods: The rate constant of force development was determined in permeabilized skeletal muscle fibers during isometric contractions evoked at free Ca²⁺ concentrations between threshold (P/P₀ = 0) and saturating (P/P₀ = 1.0) for force (P) development. The rate constant was estimated by curve fitting to the time course of isometric force redevelopment recorded after rapid release and restretch of the activated muscle fiber to disrupt cross-bridge binding. Data were obtained at 15°C in the absence or presence of NEM-S1. All values are means ± SEM.