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Tirasemtiv amplifies skeletal muscle response to nerve activation in humans.

Hansen R, Saikali KG, Chou W, Russell AJ, Chen MM, Vijayakumar V, Stoltz RR, Baudry S, Enoka RM, Morgans DJ, Wolff AA, Malik FI - Muscle Nerve (2014)

Bottom Line: The deep fibular nerve was stimulated transcutaneously to activate the tibialis anterior muscle and produce dorsiflexion of the foot.The data confirm that tirasemtiv amplifies the response of skeletal muscle to nerve input in humans.This outcome provides support for further studies of tirasemtiv as a potential therapy in conditions marked by diminished neuromuscular input.

View Article: PubMed Central - PubMed

Affiliation: Research and Early Development, Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California, 94080-4808, USA.

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Example force profiles and force–frequency response. (A) One set (of 3) normalized force profiles from a stimulation protocol. The forces (lowest to highest) were elicited with 800-ms stimulus trains of 5, 7.5, 10, 12.5, 15, 17.5, 25, and 50 Hz. The forces were normalized to the peak force elicited with 50-Hz stimulation. (B) An example of the normalized force–frequency response at a single time-point (5 hours). Peak forces (mean ± SEM) from each of the 3 replicates at each stimulation frequency were normalized to the 50-Hz average peak force.
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fig01: Example force profiles and force–frequency response. (A) One set (of 3) normalized force profiles from a stimulation protocol. The forces (lowest to highest) were elicited with 800-ms stimulus trains of 5, 7.5, 10, 12.5, 15, 17.5, 25, and 50 Hz. The forces were normalized to the peak force elicited with 50-Hz stimulation. (B) An example of the normalized force–frequency response at a single time-point (5 hours). Peak forces (mean ± SEM) from each of the 3 replicates at each stimulation frequency were normalized to the 50-Hz average peak force.

Mentions: An example of forces elicited with stimulus frequencies from 5 to 50 Hz and the resulting force–frequency relationship from a subject after placebo treatment is shown in Figure 1. Stimulation frequencies ranged from 5 Hz, where there was little or no summation of individual muscle twitches, up to 50 Hz, where the maximum force was observed. The force–frequency response was steepest around 10 Hz, which is close to the minimal discharge rate of single motor units in this muscle.8,11,12


Tirasemtiv amplifies skeletal muscle response to nerve activation in humans.

Hansen R, Saikali KG, Chou W, Russell AJ, Chen MM, Vijayakumar V, Stoltz RR, Baudry S, Enoka RM, Morgans DJ, Wolff AA, Malik FI - Muscle Nerve (2014)

Example force profiles and force–frequency response. (A) One set (of 3) normalized force profiles from a stimulation protocol. The forces (lowest to highest) were elicited with 800-ms stimulus trains of 5, 7.5, 10, 12.5, 15, 17.5, 25, and 50 Hz. The forces were normalized to the peak force elicited with 50-Hz stimulation. (B) An example of the normalized force–frequency response at a single time-point (5 hours). Peak forces (mean ± SEM) from each of the 3 replicates at each stimulation frequency were normalized to the 50-Hz average peak force.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260123&req=5

fig01: Example force profiles and force–frequency response. (A) One set (of 3) normalized force profiles from a stimulation protocol. The forces (lowest to highest) were elicited with 800-ms stimulus trains of 5, 7.5, 10, 12.5, 15, 17.5, 25, and 50 Hz. The forces were normalized to the peak force elicited with 50-Hz stimulation. (B) An example of the normalized force–frequency response at a single time-point (5 hours). Peak forces (mean ± SEM) from each of the 3 replicates at each stimulation frequency were normalized to the 50-Hz average peak force.
Mentions: An example of forces elicited with stimulus frequencies from 5 to 50 Hz and the resulting force–frequency relationship from a subject after placebo treatment is shown in Figure 1. Stimulation frequencies ranged from 5 Hz, where there was little or no summation of individual muscle twitches, up to 50 Hz, where the maximum force was observed. The force–frequency response was steepest around 10 Hz, which is close to the minimal discharge rate of single motor units in this muscle.8,11,12

Bottom Line: The deep fibular nerve was stimulated transcutaneously to activate the tibialis anterior muscle and produce dorsiflexion of the foot.The data confirm that tirasemtiv amplifies the response of skeletal muscle to nerve input in humans.This outcome provides support for further studies of tirasemtiv as a potential therapy in conditions marked by diminished neuromuscular input.

View Article: PubMed Central - PubMed

Affiliation: Research and Early Development, Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California, 94080-4808, USA.

Show MeSH