Cellular and Whole Muscle Studies of Activity Dependent Potentiation

Abstract

With a single activation, a skeletal muscle fiber, motor unit or whole muscle will yield a twitch contraction. The twitch is not an “all-or-none” response, but a submaximal response that can vary from one time to another. Prior activation causes myosin regulatory light chain (RLC) phosphorylation, by an enzyme called myosin light chain kinase. This phosphorylation dissipates slowly over the next several minutes due to a slow activity of light chain phosphatase. Phosphorylation of the RLC increases the mobility of the S1 head of myosin, bringing the S1 head in closer proximity to the myosin binding sites on actin. This increased mobility increases the rate of engagement of cross-bridges and increases the rate of force development and contraction magnitude on subsequent twitch or other submaximal contractions. We call this increased contractile response “activity dependent potentiation”. With sequential twitches or incompletely fused tetanic contractions, the term staircase is used to describe the progressive increase in amplitude of contraction. If a twitch is elicited after a tetanic contraction, we call the enhanced response posttetanic potentiation. Stretching a muscle fiber to a longer length will also bring the actin filaments close to the myosin heads. This increases the Ca²⁺ sensitivity, independent of RLC phosphorylation. At long sarcomere lengths, the impact of RLC phosphorylation is diminished, because Ca²⁺ sensitivity is already increased. Similarly, lowering the temperature at which the muscle is tested increases Ca²⁺ sensitivity. At low temperatures, staircase and posttetanic potentiation are diminished, but RLC phosphorylation still occurs. Activity dependent potentiation is an important functional modulator of contractile response.