Interaction of theophylline, verapamil, and diltiazem on hamster diaphragm muscle force in vitro.

The effect of the calcium channel blocker verapamil (5 microM) or diltiazem (5 microM) on force production and resting membrane potential (Em) was studied in the hamster diaphragm muscle. The calcium channel blockers decreased force at high frequencies of stimulation and decreased Em by 3 +/- 1 mV. The interaction of theophylline and the calcium channel blockers was also studied. When given simultaneously, the calcium channel blockers prevented the increase in force at high frequencies with theophylline at 1 mM and at all frequencies with theophylline at 0.55 mM. There was no change in Em when theophylline and calcium channel blockers were given together. Similar results were obtained by removing external calcium. The decrease in force produced by verapamil was not reversed by subsequent addition of theophylline. Theophylline did reverse the decrease in force produced by diltiazem. Verapamil reversed the increase in force at high frequencies produced by theophylline. Diltiazem reversed the force increase at low frequencies as well. These studies suggest that extracellular calcium is important in skeletal muscle contractility especially at high frequencies. Extracellular calcium is also important for the potentiation of force and the hyperpolarization of the Em produced by theophylline. The mechanism by which extracellular calcium contributes to these actions of theophylline is not known.