Fatigue from high- and low-frequency muscle stimulation: role of sarcolemma action potentials

This study compared the effect of high- (75 Hz, 1 min) and low- (5 Hz, 1.5 min) frequency stimulation on sarcolemmal action potentials of rat phrenic nerve-diaphragm preparations, measured in vitro at 25 degrees C. High-frequency stimulation reduced peak tetanic tension to 21 +/- 1% (means +/- SE) of initial, whereas 5 Hz stimulation produced less of a decline (71 +/- 2% of initial). Despite an initial faster rate of force recovery after 75-Hz stimulation, tetanic tension was still significantly depressed at 0.25 and 1 min relative to the values after 5-Hz stimulation (P less than 0.05). Resting membrane potential, and action potential overshoot and area were not significantly altered by fatigue. Action potential amplitude (AMP) was initially depressed by repetitive stimulation but increased significantly during recovery (P less than 0.05). No significant difference occurred in AMP recovery between the high- vs. low-frequency stimulation groups. The rate of rise and fall of the action potential was reduced after fatiguing stimulation but increased significantly with time (P less than 0.05). Moreover, the time to peak height of the action potential was prolonged by fatigue but significantly declined to resting values with time (P less than 0.05). During recovery, fatigue from high-frequency stimulation was associated with a greater prolongation in duration and time to baseline of the action potential relative to low-frequency stimulation (P less than 0.05). Action potential variables altered by stimulation generally recovered within 1 to 3 min, whereas peak tetanic tension did not completely return to resting values until 10 to 15 min of recovery. We conclude that high- and low-frequency stimulation elicits virtually identical perturbations in sarcolemmal action potentials, and thus changes in surface membrane properties cannot explain the decreased tetanic tension that follows 75-Hz stimulation. It appears that events distal to the sarcolemma are responsible for fatigue from both high- and low-frequency stimulation.