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Electrical stimulation (ES) of skeletal muscle partially mimics the benefits of physical activity. However, the stimulation protocols applied clinically to date, often cause unpleasant symptoms and muscle fatigue. Here, we compared the efficiency of a 'noisy' stimulus waveform derived from human electromyographic (EMG) muscle patterns, with stereotyped 45 and 1 Hz electrical stimulations applied to mouse myotubes in vitro. Human gastrocnemius medialis electromyograms recorded from volunteers during real locomotor activity were used as a template for a noisy stimulation, called EMG stim. The stimulus-induced electrical activity, intracellular Ca dynamics and mechanical twitches in the myotubes were assessed using whole-cell perforated patch-clamp, Ca imaging and optical visualization techniques. EMG stim was more efficient in inducing myotube cell firing, [Ca] changes and contractions compared with more conventional electrical stimulation. Its stimulation strength was also much lower than the minimum required to induce contractions via stereotyped stimulation protocols. We conclude that muscle cells in vitro can be more efficiently depolarized using the 'noisy' stochastic stimulation pattern, EMG stim, a finding that suggests a way to favor a higher level of electrical activity in a larger number of cells. [ABSTRACT FROM AUTHOR]