Muscle insensitivity to tetrodotoxin: induction by alpha-bungarotoxin and removal by submechanical threshold stimulation.

Intramuscular injection of alpha-bungarotoxin (alphaBGT) into rat extensor digitorum longus muscles produced pharmacological blockade of neuromuscular transmission and resulted in denervation-like changes (Berg, D. and Hall, Z. (1975), J. Physiol. (London) 244:659-676). More than 80% of fibers from alphaBGT-injected muscles produced action potentials (ap's) in the presence of tetrodotoxin (TTX, 1 X 10(-6) M). Chronic electrical stimulation of these muscles, below the level necessary to elicit a contraction, resulted in a marked return toward normal of sarcolemmal sensitivity to TTX. After 4 days of submechanical threshold stimulation, less than 45% of alphaBGT-injected fibers produced ap's in the presence of TTX, whereas more than 80% of unstimulated fibers from contralateral control muscles exhibited resistance to TTX. These findings indicate that in addition to sarcolemmal sensitivity to acetylcholine, sensitivity of the sodium conductance mechanism to TTX is also directly influenced by muscle activity independent of contraction.