On the rate-limiting dynamics of force development in muscle
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Skeletal muscles produce forces relatively slowly compared to the action potentials that excite them. The dynamics of force production are governed by multiple processes, such as calcium activation, cycling of crossbridges between myofilaments, and contraction against elastic tissues and the body. These processes have been included piecemeal in some muscle models, but not integrated to reveal which are the most rate limiting. We therefore examined their integrative contributions to force development in two conventional types of muscle models—Hill-type and crossbridge. We found that no combination of these processes can self-consistently reproduce classic data such as twitch and tetanus. Rather, additional dynamics are needed following calcium activation and facilitating crossbridge cycling, such as for cooperative myofilament interaction and reconfiguration. We provisionally lump such processes into a simple first-order model of “force facilitation dynamics” that integrate into a crossbridge-type muscle model. The proposed model self-consistently reproduces force development for a range of excitations including twitch and tetanus and electromyography-to-force curves. The model’s step response reveals relatively small timing contributions of calcium activation (3%), crossbridge cycling (3%), and contraction (27%) to overall force development of human quadriceps, with a remainder (67%) explained by force facilitation. The same set of model parameters predicts the change in force magnitude (gain) and timing (phase delay) as a function of excitatory firing rate, or as a function of cyclic contraction frequency. Although experiments are necessary to reveal the dynamics of muscle, integrative models are useful for identifying the main rate-limiting processes.
Summary statement
Muscles produce forces relatively slowly, not explained by conventional muscle processes. Quantitative modeling suggests that an intermediate process facilitating force development may be rate limiting.