SpillOver stimulation: A novel hypertrophy model using co-contraction of the plantar-flexors to load the tibial anterior muscle in rats

Abstract

The influence of loading on muscular hypertrophy has previously been studied in rodents by removal of synergistic muscles or various weight-lifting regimes. We present a novel model, evoking hypertrophy in the ratʹs tibialis anterior (TA) muscle by means of an implanted single channel electrical nerve stimulator. The amount of load experienced by the TA was measured in acute experiments in anaesthetized rats with contractions over a range of stimulation frequency and amplitude. A novel electrode configuration allowed us to elicit concentric, isometric and eccentric contractions within the same setup. This was achieved by ‘SpillOver’ stimulation in which we adjusted the amount of co-activation of the stronger antagonistic plantarflexors by increasing the stimulus above the level that caused full recruitment of the dorsiflexor muscles. The effect of loading on hypertrophy of the TA was tested in 3–4 week stimulation experiments in two groups of freely-moving rats, with a protocol that resembles typical resistance-training in humans. One group performed concentric contractions with no antagonistic co-contraction (unloaded, UNL, n = 5). In the other group the TA was loaded by simultaneous co-contraction of the antagonistically acting plantarflexors (SpillOver, n = 5). The wet mass of the stimulated TA increased in both groups; by 5.4 ± 5.5% for the UNL-group and 13.9 ± 2.9% for the SpillOver-group, with significantly greater increase in the SpillOver-group (p<0.05). Our results correlate well with values reported in literature, demonstrating that SpillOver-stimulation is a suitable model in which to study muscular hypertrophy. Even higher gains in muscle-mass may be possible by optimizing and adjusting the stimulation parameters according to the principles of progressive resistance training.

UBR5 is a novel E3 ubiquitin ligase involved in skeletal muscle hypertrophy and recovery from atrophy

“…Daily stimulation was conducted under no anaesthesia and amplitude of nerve stimulation was remotely adjusted under careful observation to provide motor neuron activation without limb withdrawal or signs of distress. Following 4 weeks of the above regime, there was an average increase of 14% in muscle weight and a 19% increase in fibre CSA in the TA muscle at the mid-belly, as described previously (Schmoll et al 2018). DNA and RNA was isolated from TA muscle originating from the aforementioned study for both the stimulated and contralateral (unstimulated) control limbs (n = 4), at rest, at the end of the 4 week electrical stimulation protocol.…”

“…In an attempt to further support these findings, we reanalysed samples from an in vivo rat model of chronic intermittent electrical stimulation‐induced hypertrophy, alongside a 14% increase in muscle weight of the TA (Schmoll et al . ). We confirmed a similar trend as after human hypertrophy demonstrated previously (Seaborne et al .…”

“…Following 4 weeks of the above regime, there was an average increase of 14% in muscle weight and a 19% increase in fibre CSA in the TA muscle at the mid‐belly, as described previously (Schmoll et al . ). DNA and RNA was isolated from TA muscle originating from the aforementioned study for both the stimulated and contralateral (unstimulated) control limbs ( n = 4), at rest, at the end of the 4 week electrical stimulation protocol.…”

UBR5 is a Novel E3 Ubiquitin Ligase involved in Skeletal Muscle Hypertrophy and Recovery from Atrophy

“…The stimulation consisted of an intermittent regime of high frequency (100 Hz) stimulation once a day for 4 weeks (5 sets x 10 reps, each rep 2s with 2s rest between reps, and 2.5 minutes rest between sets). Following 4 weeks of the above regime there was an average 14% increase in muscle weight and an 19% increase in fiber CSA in the TA muscle at the mid-belly as previously described (Schmoll et al, 2018). DNA and RNA was isolated from TA muscle from this original study (Schmoll et al, 2018)…”

“…Following 4 weeks of the above regime there was an average 14% increase in muscle weight and an 19% increase in fiber CSA in the TA muscle at the mid-belly as previously described (Schmoll et al, 2018). DNA and RNA was isolated from TA muscle from this original study (Schmoll et al, 2018)…”