Potentiation of indirectly induced muscle twitches by organic calcium antagonists in phrenic nerve-diaphragm muscle preparations of mice.

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Abstract
Organic calcium antagonists (l- and d-verapamil, D600, and diltiazem) were examined for their effects on muscle twitches of isolated phrenic nerve-diaphragm muscle preparations of mice. The calcium antagonists (1×10-6 to 7.5×10-5 M) increased the amplitude of muscle twitches induced by nerve stimuli with short durations (0.04 to 0.4 msec) of rectangular pulses. However, these agents were poorly effective on twitches induced by nerve stimuli with longer durations over 0.6 msec or by direct shocks. The potentiative effect was reversible, reproducible and dependent on their concentrations. Diltiazem was the most effective among the four agents tested. The twitch increase produced by all of the agents was demonstrated at concentrations of external Ca++ above 0.6 mM. At Ca++ concentrations below 0.5 mM, the tension of the indirectly induced muscle twitch was partially inhibited in the presence of these agents. Caffeine, theophylline, isoproterenol or hypertonic potassium ions increased the tension of indirectly induced muscle twitches. The potentiative effect of the organic calcium antagonists, however, was discriminated from those induced by the other agents under some conditions. From these results, it is suggested that the organic calcium antagonists alter the reactivity of the preparation to nerve shock. The potentiative effect of the agents on indirectly induced muscle twitch may include an increase in the number of fibers contracting per nerve impulse through increasing transmitter release from the nerve terminal, but not an increase in contractility of an individual muscle fiber.

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