Slowing of relaxation in the fatiguing hamster diaphragm is enhanced by theophylline

Hamster diaphragm muscle strips were treated with theophylline (100 mg/l) or caffeine (100 mg/l) to study the effect on the time constant of relaxation (tau) during repeated contractions and with recovery. Two stimulation protocols were used: a high-tension time index (TTI, 60 Hz, 160 ms, 2/s) and a low TTI (25 Hz, 160 ms, 1/s). In the high TTI protocol an early increase in the tau was noted in theophylline but not in caffeine or control. In the low TTI protocol there was no difference in tau with theophylline. The combination of theophylline (100 mg/l) and verapamil (5 microM) was also studied. Verapamil decreased force in contractions of 300-ms duration but not in those lasting 160 ms and had no effect on tau. It did not block the prolongation of tau seen with theophylline. These studies suggest that theophylline has a direct effect on relaxation of skeletal muscle, which is not prevented by verapamil, and also that external calcium may be important for sustained contractions of skeletal muscle.