myoneural effects of verapamil on the rat phrenic nerve-diaphragm preparation

ABSTRACT

The effects of verapamil on the neuromuscular transmission and muscular contraction were studied using isolated phrenic nerve diaphragm preparation. The diaphragmatic contractions elicited by either indirect or direct electrical stimulation were inhibited by verapamil. The inhibitory effect of verapamil was greater with indirect than direct stimulation. Verapamil was found to be capable to enhance the paralysis of the indirectly stimulated rat diaphragm induced by either d-tubocurarine or succinylcholine. The combination of verapamil and d-tubocurarine- led to a synergistic inhibition of the neuromuscular transmission, while the combination of verapamil and succinylcholine led to additive inhibition. Pretreatment with verapamil abolished and markedly inhibited the stimulant effects of digoxin on the indirectly and directly induced diaphragmatic -contractions respectively. Doubling the concentration of calcium in the bathing fluid produced no change in the inhibitory effects of verapamil on either indirectly or directly elicited diaphragmatic contractions. Pretreatment with 4-aminopyridine suppressed the inhibitory effects of verapamil on diaphragmatic contractions elicited either indirectly or directly, while pretreatment with adenosine enhanced the inhibitory effect of verapamil on diaphragmatic contractions elicited by indirect electrical stimulation. The enhancement effects of aminophylline and forskolin on the contractions of rat diaphragm induced either indirectly or directly were abolished and markedly inhibited respectively by pretreatment with verapamil. Pretreatment with verapamil markedly inhibited the enhancement effect of caffeine on diaphragmatic contractions induced indirectly, but did not change the enhancement effect of caffeine on directly induced contractions. It is concluded that verapamil acts by a -mixture of pre-and postsynaptic effects to inhibit the neuromuscular transmission and acts at the muscle membrane to inhibit the muscular contraction