Excitation of Skeletal Muscle by Fluoride

Abstract

The effects of NaF on the mechanical and electrical responses of sciatic nerve-sartorius muscle preparations from the bullfrog were investigated in an attempt to elucidate the mechanism of excitation of skeletal muscle induced by fluoride. NaF at concentrations above 0.1 mM augmented the twitch and tetanus evoked by indirect stimulation of the partially fatigued muscle, and above 5.0 mM it induced fibrillation. Sodium oxalate at 2.5 mM, sodium citrate at 1.7 mM, and calcium-deficient Ringer's solution neither induced fibrillation nor augmented the twitch. NaF increased the amplitude of the miniature endplate potential (m.e.p.p.) even under pre-treatment with 16 μM neostigmine, but the extent of the increment was only one half as much as that by NaF alone. NaF, 0.1 mM adrenaline, 1.0 mM theophylline, and 4.0 mM dibutyryl cyclic AMP, raised the m.e.p.p. frequency and increased the quantal content of the endplate potential. These findings suggest that fluoride may induce excitation of skeletal muscle in a manner unrelated to decalcification and that such excitation may be due to the activation of adenylate cyclase in the nerve ending, the inhibition of cholinesterase, and to increased sensitivity of the endplate to acetylcholine.