K⁺-induced twitch potentiation is not due to longer action potential

Abstract

The objective of this study was to determine whether an increased duration of the action potential contributes to the K+-induced twitch potentiation at 37 degrees C. Twitch contractions were elicited by field stimulation, and action potentials were measured with conventional microelectrodes. For mouse extensor digitorum longus (EDL) muscle, twitch force was greater at 7-13 mM K+ than at 4.7 mM (control). For soleus muscle, twitch force potentiation was observed between 7 and 11 mM K+. Time to peak and half-relaxation time were not affected by the increase in extracellular K+ concentration in EDL muscle, whereas both parameters became significantly longer in soleus muscle. Decrease in overshoot and prolongation of the action potential duration observed at 9 and 11 mM K+ were mimicked when muscles were respectively exposed to 25 and 50 nM tetrodotoxin (TTX; used to partially block Na+ channels). Despite similar action potentials, twitch force was not potentiated by TTX. It is therefore suggested that the K+-induced potentiation of the twitch in EDL muscle is not due to a prolongation of the action potential and contraction time, whereas a longer contraction, especially the relaxation phase, may contribute to the potentiation in soleus muscle.

Changes of action potentials and force at lowered [Na+]o in mouse skeletal muscle: implications for fatigue

“…A striking observation from the present study is that the overshoot could fall by almost 30 mV without any depression of peak twitch force (Fig. 8) (32). Because the decreases in overshoot during fatigue are Ͻ30 mV (18), our data suggest that changes in overshoot (or action potential peak) are unlikely to cause fatigue.…”

“…It has often been suggested that any decrease in action potential amplitude reduces the amount of Ca 2ϩ released by the sarcoplasmic reticulum. However, using tetrodotoxin, Yensen et al (32) recently showed that the peak twitch force of mouse EDL does not decrease until the overshoot becomes Ͻ10 mV. It remains to be determined whether the same relationship can be observed when the Na ϩ gradient is reduced.…”

Skeletal muscle fatigue – regulation of excitation–contraction coupling to avoid metabolic catastrophe

“…In vitro at 37˚C, maximal tetanic force is not affected until the [K + ] e reaches 10 mM; at or above that concentration, tetanic force decreases (Cairns et al, 2011). Twitch and submaximal tetanic forces, are potentiated when [K + ] e is increased up to 12 mM (Holmberg and Waldeck, 1980), whereas above that concentration twitch force is depressed (Yensen et al, 2002). The mechanism of the K + -induced potentiation is unknown, but is no doubt beneficial for maximizing muscle performance at the onset of exercise.…”

“…The mechanism of the K + -induced potentiation is unknown, but is no doubt beneficial for maximizing muscle performance at the onset of exercise. The K + -induced force depression, on the other hand, is due to a K + -induced depolarization of the cell membrane resulting in decreased action potential overshoot as Na + channels are inactivated (Yensen et al, 2002) (Fig. 3; Box 3).…”

“…3; Box 3). There is indirect evidence that the amount of Ca 2+ that is released by SR is reduced once the action potential overshoot decreases below 5 mV; twitch force is unaffected when overshoot varies between 5 and 30 mV (Cairns et al, 2003;Yensen et al, 2002). It is also important to note that the force-[K + ] e relationship is dynamic; i.e.…”