Doublet discharge stimulation increases sarcoplasmic reticulum Ca 2+ release and improves performance during fatiguing contractions in mouse muscle fibres

Key points Motor neurons are frequently activated to give two action potentials at 200–300 Hz (doublets) at the onset of voluntary contractions. Doublets increase force and rate of force development. During fatigue, decreased sarcoplasmic reticulum Ca 2+ release and decreased myofibrillar Ca 2+ sensitivity both contribute to the fatigue‐induced force loss. We studied whether electrically evoked doublets at contraction onset can counteract such fatigue‐induced changes. Experiments were performed using intact fast‐twitch and slow‐twitch single muscle fibres of mice. In the unfatigued state, doublets induce increased sarcoplasmic reticulum Ca 2+ release at the onset of contractions, which increases peak force and force–time integral. During fatigue induced by 150 repeated contractions, doublets markedly improve isometric force production during the first 25 contractions. At the end of fatigue, addition of doublets at contraction onset can temporarily increase force production. Doublets are beneficial in that they improve contractile performance when added at any stage of strenuous activity, although the effect is largest in early fatigue stages. Abstract Double discharges (doublets) of motor neurones at the onset of contractions increase both force and rate of force development during voluntary submaximal contractions. The purpose of this study was to examine the role of doublet discharges on force and myoplasmic free [Ca 2+ ] ([Ca 2+ ] i ) during repeated fatiguing contractions, using a stimulation protocol mimicking the in vivo activation pattern during running. Individual intact fibres from the flexor digitorum brevis muscle of mice were stimulated at 33°C to undergo 150 constant–frequency (five pulses at 70 Hz) or doublet (an initial, extra pulse at 200 Hz) contractions at 300 ms intervals. In the unfatigued state, doublet stimulation resulted in a transient (∼10 ms) approximate doubling of [Ca 2+ ] i , which was accompanied by a greater force–time integral (∼70%) and peak force (∼40%) compared to constant frequency contractions. Moreover, doublets markedly increased force–time integral and peak force during the first 25 contractions of the fatiguing stimulation. In later stages of fatigue, addition of doublets increased force production but the increase in force production corresponded to only a minor portion of the fatigue‐induced reduction in force. In conclusion, double discharges at the onset of contractions effectively increase force production, especially in early stages of fatigue. This beneficial effect occurs without additional force loss in later stages of fatigue, indicating that the additional energy cost induced by doublet discharges to skeletal muscle is limited.