Interactions between suxamethonium and non-depolarizing neuromuscular blocking drugs

In anaesthetized cats, we have confirmed that previously injectedsuxamethonium potentiates non-depolarizing neuromuscular blockingdrugs whereas, when injected during the block, suxamethoniumantagonizes the paralysis. We have attempted to explain theseinteractions by studying the effects of suxamethonium on extracellularlyrecorded nerve ending waveforms that correspond to the ioniccurrents in the mouse triangularis sterni isolated nerve-musclepreparation. The preparations were paralysed with µ-conotoxin(obtained from the cone snail), which is believed to act byselectively blocking sodium channels in muscle, and which thereforeshould not interfere with currents at the nerve endings. Suxamethonium,in concentrations of 0.5-300 µmol litre^–1, produceda concentration-dependent increase in the amplitude of the waveformcorresponding to the inward calcium current evoked by a nerveimpulse. This effect did not occur in the presence of tubocurarine,suggesting that suxamethonium, which is a nicotinic agonist,may have been acting on a nicotinic receptor on the nerve endingsthat is coupled to the voltage-operated calcium channels. Theinward calcium current is believed to be responsible for neurotransmitter(acetylcholine) release. It is concluded, therefore, that itsenhancement by suxamethonium contributes to the ability of thisdrug to reverse non-depolarizing block. Suxamethonium also exertedcomplex effects on the waveform corresponding to the outwardflowing calcium-activating potassium current at the nerve endings,but no effect was observed in this isolated nerve-muscle preparationthat could obviously explain the ability of suxamethonium topotentiate subsequently injected non-depolarizing blocking drugs.