抄録
Botulinum neurotoxin (BoNT) inhibits neurotransmitter release at motor nerve terminals, thus paralyzing skeletal muscles. Long-term paralysis persists due to functional and structural changes of the neuromuscular junction. This is true for several skeletal muscles, but not for all diaphragmatic muscles. We used in vitro mouse diaphragm preparations to examine the effects of BoNT serotype A (BoNT/A) injected intraperitoneally on electrically activated diaphragm muscles. Both contractility and neurotransmitter release were measured at 0, 1, 2, and 4 wk after the injection. There was an increase in the amplitude of directly induced twitches (DT) throughout the observation period. Indirectly induced twitch (IT) amplitude decreased to 40% that of controls at 1 wk, which gradually began to recover during the 4-wk observation period. Spontaneous neurotransmitter release, measured as the frequency of miniature endplate potentials, was largely abolished 1 wk after the injection and recovered only slightly during the 4-wk period. The effects on spontaneous release were independent of the calcium concentration in the medium. Evoked release, measured as quantal content, was also mostly inhibited at 1 wk, but recovered to approximately 50% of controls at 4 wk. Dependency of the evoked output on external calcium concentrations had a calcium ion cooperativity value of 1.559 at 4 wk. This value was less than half that of controls, indicating improved calcium utilization at motor nerve endings exposed to BoNT/A.
