Combination of variable frequency train stimulation and K+ channel blockade to augment skeletal muscle force

Several innovative approaches are being used to optimize the input-output relationship of muscle, including nonlinear stimulation paradigms and altering muscle membrane ion channel conductances. We tested the hypothesis that the combination of the K⁺ channel blocker, 3,4-diaminopyridine (DAP), and variable frequency train (VFT) stimulation improves muscle force to a greater extent than either modality alone. Studies were done in vitro on rat diaphragm muscle and contractions were quantified with respect to peak force, mean force, and force area. DAP increased all three force parameters by >50% during conventional 10-20-Hz stimulation, whereas VFT stimulation improved contractile performance for peak force only. When combined, DAP and VFT stimulation augmented peak force to a significantly greater extent than either modality alone. However, this came at a cost of a moderate decline in force area relative to DAP alone, although mean force was preserved. These force increases were generally well-maintained over the course of short-term repetitive stimulation. Thus, VFT stimulation and K⁺ channel blockade interact in a complex manner to modulate skeletal muscle force. The utility of the combined intervention for functional electrical stimulation may be greatest for mechanical tasks requiring high force levels early during the contraction.