Effects of low calcium and calcium antagonists on skeletal muscle staircase and fatigue.

The purpose of this investigation was to determine the effects of low extracellular calcium and calcium antagonists on skeletal muscle staircase and fatigue. Initial experiments revealed that, brief exposure (10 minutes) of single frog sartorius muscle to diltiazem, D-600 (5 and 30 microM) and low calcium Ringer's solution (LCR, calcium replaced by magnesium and EGTA) had little effect on isometric twitches evoked every 30 seconds. However, when stimulated at 1 per second for 15 minutes, the calcium antagonists significantly decreased the magnitude and time course of the staircase, whereas LCR decreased only the time course. Each experimental condition significantly increased the rate of fatigue while diltiazem and D-600 both increased the magnitude of fatigue. Following the stimulation period, caffeine (10 mM) elicited contractures from all muscles whereas high potassium (180 mM) elicited contractures from control muscles only. These results indicate that calcium channel antagonists depress the skeletal muscle staircase response. They also indicate that these compounds as well as LCR enhance the fatigue process. Extracellular calcium influx may therefore have some influence on skeletal muscle twitches during prolonged repetitive activity.