Prolonged Low-frequency Force Depression Of Intact Single Mice Myofibers Is Partly Recovered With Post-Tetanic Potentiation

PURPOSE: To assess whether prolonged low-frequency force depression (PLFFD) can be mitigated by post-tetanic potentiation (PTP) in intact single mice myofibers. METHODS: Intact single myofibers of the flexor digitorum brevis muscle of C57BL6 mice (~14 weeks old, n = 9) were dissected with tendons intact, microinjected with FURA-2 to measure intracellular calcium, perfused with Tyrode’s solution (21% O2 and 5% CO2 at 32 °C) and isometric force was recorded during electrical stimulations (350 ms trains, 8 V). To establish pre-fatigue values of force and calcium, myofibers were stimulated with 30, 50, 70 and 200 Hz contractions sequentially, separated by 2 s each (force-frequency protocol, FFP). To induce PLFFD, each myofiber was stimulated with 150 Hz contractions every 3 s until force dropped to 30% of initial. At 30-min following the fatiguing task, a FFP was applied before and immediately post six 150 Hz stimulations each separated by 2 s. The force before the six 150 Hz stimulations was used to assess PLFFD, and the force recorded after was used to assess the effect of PTP during the state of PLFFD. RESULTS: Myofibers (n = 9) required 70 ± 16 (mean ± SE) contractions to induce a 70% loss of force. At 30-min following fatigue, PLFFD was evident with force responses depressed at 30, 50, and 70 Hz and were ~ 40, ~33 and ~ 60% of pre-fatigue, respectively, (all P < 0.01) compared to 200 Hz which was ~85% of pre-fatigue (P < 0.05). Following six 150 Hz stimulations (i.e, PTP during PLFFD), force in response to 30, 50, and 70 Hz were ~ 195, ~260, and ~ 165% of PLFFD values, respectively, (all P ≤ 0.001) with no change in force at 200 Hz stimulation (~96% of pre-fatigue, P > 0.05). Therefore, inducing PTP during PLFFD enhanced single myofiber force closer to pre-fatigue values for the 30 (~80%), 50 (~87%) and 70 (~95%) Hz stimulations. CONCLUSIONS: In single myofibers from mice at near-physiological temperature, inducing PTP during PLFFD enhanced force in response to low and moderate frequencies. However, PLFFD could not be fully reversed by PTP. Therefore, despite impaired force generation during PLFFD single myofibers are sensitive to activation history force enhancement. Supported by NSERC. NSERC