Sites of action of nifedipine at the neuromuscular junction

ABSTRACT

The sites of action of nifedipine at the neuromuscular junction have been determined by studying its effects on indirect, direct muscle twitches and KCl- and caffeine-induced contractures of the rat diaphragm, and its effects on the contractures produced by Ach, carbachol and KCl in the frog rectus abdominis muscle. Cumulative addition of nifedipine [15 - 150 muM] potentiated indirectly and directly evoked muscle twitches. At a stimulation frequency of 1 Hz, nifedipine produced a biphasic response expressed by a potentiation, followed by blockade of the indirect muscle twitches. In preparations kept in solution with low Ca +2 concentration [0.52 mM], the cumulative addition of nifedipine [30 - 120 muM] produced a potentiation, followed by neuromuscular blockade which was reversed by raising Ca +2 concentration. In preparations kept in Ca +2-free solution, nifedipine produced a biphasic effect on the directly evoked muscle twitches. On tetanic tension curve, nifedipine [60 muM] reduced the first phase and produced a tetanic fade of the second phase. Nifedipine [10 muM] potentiated the two phases of KCl- and caffeine- induced contractures in the rat diaphragm. Similarly, nifedipine potentiated the contractures produced by Ach and KCl but reduced that of carbachol in the rectus abdominis muscle. In conclusion, the twitch-potentiating action of nifedipine appears to be mediated at the level of the sarcoplasmic reticulum [SR] and /or cholinesterase enzyme inhibition, while the twitch-inhibitory action of nifedipine appears to be mediated at the level of motor nerve terminals