Inhibition of aminopyridine-induced contractile activity in skeletal muscle by tetrodotoxin and by magnesium.

The effects of tetrodotoxin and magnesium have been studied on aminopyridine-induced contractile activity seen in the absence of nerve stimulation. In the chick biventer cervicis muscle both tetrodotoxin and magnesium pretreatment prevented the development of fasciculations and contractures in the presence of 4-aminopyridine and 3,4-diaminopyridine. Both tetrodotoxin and magnesium abolished aminopyridine induced fasciculations and contractures. Tetrodotoxin did not reduce postjunctional sensitivity to the agonists acetylcholine and carbachol whereas magnesium produced some reduction of postjunctional sensitivity. It is concluded that conducted action potentials must be involved in the aminopyridine-induced contractile activity. In the frog sartorius muscle aminopyridines occasionally induced repetitive endplate potentials suggesting that the compounds induce repetitive nerve activity. In both tetrodotoxin and magnesium treated preparations 4-aminopyridine produced only a moderate increase in miniature endplate potential frequency. It is concluded that aminopyridines increase nerve membrane excitability resulting in the generation of repetitive action potentials in the absence of nerve stimulation.