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

Abstract

]o relationships for the twitch and tetanus were the same in nonfatigued extensor digitorum longus and soleus muscles: force was maintained over a large range of [Na ϩ ]o and then decreased abruptly over a much smaller range. However, fatigue was significantly exacerbated at a lowered [Na ϩ ]o that had little effect in nonfatigued soleus muscle. This finding suggests that substantial differences exist in the Na ϩ effect on force between nonfatigued and fatigued muscle. The reduced contractility in nonfatigued muscles at lowered [Na ϩ ]o was largely due to 1) an increased number of inexcitable fibers and threshold for action potentials, 2) a reduction of action potential amplitude, and 3) a reduced capacity to generate action potentials throughout trains. sodium gradient; muscle contraction; action potential train; extensor digitorum longus; soleus DURING REPETITIVE ACTIVATION of skeletal muscle, a net influx of sodium ions (Na ϩ

Properties of single FDB fibers following a collagenase digestion for studying contractility, fatigue, and pCa-sarcomere shortening relationship

“…In terms of viability, it is critical that isolated single fibers exhibit characteristics similar to those measured from whole muscle bundles. Here, single fibers were elicited to contract with a stimulation pulse of 0.3 ms and stimulation strength from 2 to 10 V, which are values consistent with those used to elicit contractions in intact muscles (10,11,18). Under steady-state conditions, mean resting Em was Ϫ62 mV at 25°C, which is similar to reported values for FDB fibers tested at similar temperatures (6,7,43).…”

“…Resting Em and action potentials are easily measured from the surface fibers of mouse EDL and soleus when one uses microelectrodes filled with 3 M KCl (10,28,36). In single fibers, microelectrode filled with KCl was the least effective for recording stable resting Em due to very large membrane depolarization upon penetration.…”

Skeletal Muscle Fatigue: Cellular Mechanisms

“…Typically single fibers are stimulated with plate electrodes so that the AP is simultaneously generated at multiple points along the fiber, eliminating longitudinal transmission of the AP as a possible mechanism of fatigue. Prolonged high-frequency stimulation applied focally to only one region of a muscle fiber produces greater and faster loss of force than does stimulation applied all along the length of the fiber via parallel electrodes (80,265), which may indicate that failure of longitudinal AP transmission is an important fatigue mechanism in this situation. However, this force loss may reflect methodological problems with focal electrical stimulation in in vitro experiments, and in our view, this type of failure probably does not normally occur in vivo in healthy humans (see sect.…”

“…Nevertheless, these changes to the surface AP do not appear to contribute to fatigue (28), as the AP evidently remains sufficient to initiate an AP in the T system because of the large safety factor in the process. The changes in the sarcolemmal properties and AP can also lead to intermittent failure in a train of APs (28,80), but the accompanying slowing of fusion frequency means that such AP failure does not evidently contribute to decreased force.…”

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

“…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.…”